不同转移潜能的人肝癌模型细胞膜蛋白及血清蛋白质组学研究
|
摘要
肝癌是最常见的恶性肿瘤之一,每年大约有60万人死于肝癌,居癌症死亡人数第三位。亚洲和撒哈拉以南非洲的肝癌发病率最高。由于HCV感染,估计未来10-20年西方的肝癌发病率增加2倍。对于早期和局部病灶而言,手术切除仍是可能获得治愈的主要手段。即使如此,根治术后5年的复发率仍达70%。尽管近年来在肝癌诊治和机理研究方面取得了长足的进步,临床可用的预测肝癌侵袭和转移的标志物仍然缺少。
不同转移潜能的人肝癌细胞MHCC97L和HCCLM9细胞是研究肝癌的良好模型系统。HCCLM9为肝癌高转移细胞,由体内筛选而来,MHCC97L为肝癌低转移细胞。两者遗传背景相仿,转移潜能不同。
细胞膜分隔胞内容物和外环境,在维持细胞功能方面扮演着重要的作用。膜蛋白和其他组分共同构成细胞结构,维持细胞间的运动和识别,参与结合受体,细胞内外的运输,细胞间和细胞基质间的相互作用,以及构成细胞骨架。当肿瘤生物学行为改变时,癌细胞膜蛋白的组分和特性也会发生改变,这有可能是之成为潜在的标志物。
血清是获得肿瘤标志物的理想来源。肿瘤细胞与微环境相互作用后,从原发瘤转移至远处器官。来自病灶的蛋白裂解物进入淋巴和血液,随之可能在血清和组织中检出,成为潜在的肿瘤标志物。
本研究首次采用蛋白质谱技术,分析不同转移潜能的人肝癌模型MHCC97L和HCCLM9的膜蛋白和血清,对差异蛋白进一步行动物模型及临床标本验证,旨在寻找与肝癌侵袭转移相关的靶分子。
第一部分：不同转移潜能人肝癌细胞膜蛋白质组学研究
目的采用膜蛋白质组学技术筛选与原发性肝癌侵袭和转移相关分子,并加以验证。方法以HCCLM9和MHCC97L不同转移潜能人肝癌细胞为研究对象,采用SDS-PAGE和ESI-MS/MS技术比较和鉴定差异表达的细胞膜蛋白,进一步行western blot、动物模型标本和临床标本验证。结果MHCC97L与HCCLM9相比,显著性差异表达细胞膜蛋白14个,其中coronin-1C在HCCLM9细胞表达升高2.57倍,在裸鼠肝癌组织中免疫组化提示coronin-1C表达也明显升高。115例临床病理组织免疫组化显示,coronin-1C表达越强,肿瘤的侵袭程度越强、临床病期越晚。结论coronin-1C与肝癌侵袭转移相关。
第二部分：不同转移潜能人肝癌模型血清蛋白质组学研究
目的采用血清蛋白质组学技术筛选并鉴定肝癌转移相关的蛋白分子。方法建立不同转移潜能人肝癌HCCLM9和MHCC97L动物模型各8只,采用双向凝胶电泳和MALDI串联飞行时间质谱仪(MALDI-TOF/TOF)技术比较和鉴定差异表达的血清蛋白分子,western blot和动物模型标本验证后,建立肝癌肺转移裸鼠模型,确认目的蛋白在肿瘤转移过程中的变化,进一步对208例临床标本(男性170例,女性38例)验证。结果HCCLM9和MHCC97L组相比,血清蛋白表达显著差异达11个,其中补体因子H(complement factor H, CFH)在HCCLM9模型血清中水平(213.83±55.17)比MHCC97L组(122.48±48.91)高1.75倍。血清western blot结果显示当肝癌肺转移发生时,CFH的表达达到顶峰。裸鼠肝癌组织中免疫组织化学提示CFH表达明显升高。208例临床病理组织显示,CFH表达越强,临床病期越晚。结论CFH与肝癌侵袭转移相关。
Hepatocellular carcinoma (HCC), accounting for an estimated 600,000 deaths annually, is the third leading cause of cancer-related mortality worldwide. Most cases occur in Asia and sub-Saharan Africa, however, the incidence is also expected to double over the next 10 to 20 years in the West, possibly due to the increased HCV infection. While curative therapies are possible if the lesion remains early and localized, almost 70% of resected cases recurred within 5 years. Impressive progression has been made in providing an increasingly comprehensive portrayal of HCC. However, biomarkers that indicate the risk of invasion and metastatic potential of HCC and can be widely used in clinical settings are not currently available.
For a better insight into the characteristic of HCC metastasis, the stepwise metastatic human HCC cells MHCC97L and HCCLM9, with low and high metastatic potentials, were established via repeated in vivo selection and characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior, providing appropriate model systems for comparative study on the molecular events correlated with HCC metastasis.
Plasma membrane, the structure surrounding all living cells and acting as the primary interface between the cellular contents and the extracellular environment, plays crucial roles in cell functions. Membrane proteins and other components maintain cell structure, motility and recognition involved in receptor-binding and further transport of bound components into the cell, cell-cell and cell-matrix interactions, and the organization of the cytoskeleton. The composition and characteristics of membrane proteins of tumor cells are modified during malignant transformation and make them likely candidates for cancer biomarkers.
Serum and tissue are optimal sources for discovery and analysis of cancer biomarker. Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Proteins derived from diseased tissue compartments may leak into lymph and blood, eventually becoming detectable in serum and tissues and representing potential biomarkers of disease.
The current work was firstly to identify potential proteins from cell membrane and serum related to HCC invasive progression, using human HCC cells with different metastasis potentials, by proteomics analysis, experimental animal studies and clinical validation.
Part One:Proteome analysis of cell membrane from hepatocellular carcinoma model system with multiple metastatic potentials
Objective To search for hepatocellular carcinoma (HCC) invasion and metastasis related biomarkers using the cell membrane proteomics approaches, and to validate the markers using experimental and clinical specimens. Methods HCCLM9 and MHCC97L cell, with a similar genetic background and remarkably different metastasis behaviors, were used for comparative membrane proteome profiling using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electrospray ionization mass spectrometry (ESI-MS) technologies. Candidate protein makers were further validated by Western blot on cells, immunohistochemistry (IHC) on animal tumor tissues, and tissue micro-array on clinical specimens. Results Membrane proteins from MHCC97L and HCCLM9 cells were compared by SDS-PAGE analyses. A total of 14 proteins were identified by ESI-MS/MS among the differential bands. Coronin-1C was overexpressed in HCCLM9 (7.31±0.73) versus MHCC97L (2.84±0.99), and validated by western blot and IHC from both nude mice tumor tissues and clinical specimens. Elevated coronin-1C expression was observed in liver cancer tissues of HCCLM9 nude mice. IHC study in 115 human HCC specimens demonstrated that patients with higher coronin-1C expession showed greater invasiveness and more advanced stage. Conclusion The study suggests coronin-1C could be a candidate biomarker to predict HCC invasive behavior.
Part One:Proteome analysis of serum from hepatocellular carcinoma model system with multiple metastatic potentials
Objective Serum proteomics approaches were applied to search for and validate hepatocellular carcinoma (HCC) invasion and metastasis related biomarkers. Methods 16 male athymic BALB/c nu/nu mice were randomly divided into two groups. HCCLM9-and MHCC97L-nude mice models of human HCC, with a similar genetic background and remarkably different pulmonary metastasis potential, were established.2D gel electrophoresis (2-DE) and MALDI-TOF/TOF technologies were used to construct a comparative proteome profile of nude mice sera from HCCLM9-and MHCC97L-nude mice. Candidate protein was confirmed by western blot and measured in sera from tumor development of spontaneous pulmonary metastasis in HCCLM9-nude mice. This result was further was analyzed by immunohistochemistry (IHC) on animal tumor tissues, and tissue micro-array on clinical specimens including 170 male cases and 38 female cases. Results Serum proteins from HCCLM9-and MHCC97L-nude mice were compared by 2-DE. A total of 11 proteins were identified by MALDI-TOF/TOF. Complement factor H (CFH) was overexpressed in HCCLM9-(213.83±55.17) versus MHCC97L-nude mice serum (122.48±48.91) by western blot, and validated by IHC from both nude mice tumor tissues and clinical specimens. Serum CFH level showed a remarkable upsurge when pulmonary metastasis occurred. Elevated CFH expression was observed in liver cancer tissues of HCCLM9 nude mice. IHC study in 208 human HCC specimens including demonstrated that patients with higher CFH expession showed greater invasiveness and more advanced stage. Conclusion The study suggests CFH could be a candidate biomarker to predict HCC invasive behavior.
不同转移潜能的人肝癌细胞MHCC97L和HCCLM9细胞是研究肝癌的良好模型系统。HCCLM9为肝癌高转移细胞,由体内筛选而来,MHCC97L为肝癌低转移细胞。两者遗传背景相仿,转移潜能不同。
细胞膜分隔胞内容物和外环境,在维持细胞功能方面扮演着重要的作用。膜蛋白和其他组分共同构成细胞结构,维持细胞间的运动和识别,参与结合受体,细胞内外的运输,细胞间和细胞基质间的相互作用,以及构成细胞骨架。当肿瘤生物学行为改变时,癌细胞膜蛋白的组分和特性也会发生改变,这有可能是之成为潜在的标志物。
血清是获得肿瘤标志物的理想来源。肿瘤细胞与微环境相互作用后,从原发瘤转移至远处器官。来自病灶的蛋白裂解物进入淋巴和血液,随之可能在血清和组织中检出,成为潜在的肿瘤标志物。
本研究首次采用蛋白质谱技术,分析不同转移潜能的人肝癌模型MHCC97L和HCCLM9的膜蛋白和血清,对差异蛋白进一步行动物模型及临床标本验证,旨在寻找与肝癌侵袭转移相关的靶分子。
第一部分：不同转移潜能人肝癌细胞膜蛋白质组学研究
目的采用膜蛋白质组学技术筛选与原发性肝癌侵袭和转移相关分子,并加以验证。方法以HCCLM9和MHCC97L不同转移潜能人肝癌细胞为研究对象,采用SDS-PAGE和ESI-MS/MS技术比较和鉴定差异表达的细胞膜蛋白,进一步行western blot、动物模型标本和临床标本验证。结果MHCC97L与HCCLM9相比,显著性差异表达细胞膜蛋白14个,其中coronin-1C在HCCLM9细胞表达升高2.57倍,在裸鼠肝癌组织中免疫组化提示coronin-1C表达也明显升高。115例临床病理组织免疫组化显示,coronin-1C表达越强,肿瘤的侵袭程度越强、临床病期越晚。结论coronin-1C与肝癌侵袭转移相关。
第二部分：不同转移潜能人肝癌模型血清蛋白质组学研究
目的采用血清蛋白质组学技术筛选并鉴定肝癌转移相关的蛋白分子。方法建立不同转移潜能人肝癌HCCLM9和MHCC97L动物模型各8只,采用双向凝胶电泳和MALDI串联飞行时间质谱仪(MALDI-TOF/TOF)技术比较和鉴定差异表达的血清蛋白分子,western blot和动物模型标本验证后,建立肝癌肺转移裸鼠模型,确认目的蛋白在肿瘤转移过程中的变化,进一步对208例临床标本(男性170例,女性38例)验证。结果HCCLM9和MHCC97L组相比,血清蛋白表达显著差异达11个,其中补体因子H(complement factor H, CFH)在HCCLM9模型血清中水平(213.83±55.17)比MHCC97L组(122.48±48.91)高1.75倍。血清western blot结果显示当肝癌肺转移发生时,CFH的表达达到顶峰。裸鼠肝癌组织中免疫组织化学提示CFH表达明显升高。208例临床病理组织显示,CFH表达越强,临床病期越晚。结论CFH与肝癌侵袭转移相关。
Hepatocellular carcinoma (HCC), accounting for an estimated 600,000 deaths annually, is the third leading cause of cancer-related mortality worldwide. Most cases occur in Asia and sub-Saharan Africa, however, the incidence is also expected to double over the next 10 to 20 years in the West, possibly due to the increased HCV infection. While curative therapies are possible if the lesion remains early and localized, almost 70% of resected cases recurred within 5 years. Impressive progression has been made in providing an increasingly comprehensive portrayal of HCC. However, biomarkers that indicate the risk of invasion and metastatic potential of HCC and can be widely used in clinical settings are not currently available.
For a better insight into the characteristic of HCC metastasis, the stepwise metastatic human HCC cells MHCC97L and HCCLM9, with low and high metastatic potentials, were established via repeated in vivo selection and characterized by a similar genetic background but with significant differences in spontaneous metastasis behavior, providing appropriate model systems for comparative study on the molecular events correlated with HCC metastasis.
Plasma membrane, the structure surrounding all living cells and acting as the primary interface between the cellular contents and the extracellular environment, plays crucial roles in cell functions. Membrane proteins and other components maintain cell structure, motility and recognition involved in receptor-binding and further transport of bound components into the cell, cell-cell and cell-matrix interactions, and the organization of the cytoskeleton. The composition and characteristics of membrane proteins of tumor cells are modified during malignant transformation and make them likely candidates for cancer biomarkers.
Serum and tissue are optimal sources for discovery and analysis of cancer biomarker. Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Proteins derived from diseased tissue compartments may leak into lymph and blood, eventually becoming detectable in serum and tissues and representing potential biomarkers of disease.
The current work was firstly to identify potential proteins from cell membrane and serum related to HCC invasive progression, using human HCC cells with different metastasis potentials, by proteomics analysis, experimental animal studies and clinical validation.
Part One:Proteome analysis of cell membrane from hepatocellular carcinoma model system with multiple metastatic potentials
Objective To search for hepatocellular carcinoma (HCC) invasion and metastasis related biomarkers using the cell membrane proteomics approaches, and to validate the markers using experimental and clinical specimens. Methods HCCLM9 and MHCC97L cell, with a similar genetic background and remarkably different metastasis behaviors, were used for comparative membrane proteome profiling using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electrospray ionization mass spectrometry (ESI-MS) technologies. Candidate protein makers were further validated by Western blot on cells, immunohistochemistry (IHC) on animal tumor tissues, and tissue micro-array on clinical specimens. Results Membrane proteins from MHCC97L and HCCLM9 cells were compared by SDS-PAGE analyses. A total of 14 proteins were identified by ESI-MS/MS among the differential bands. Coronin-1C was overexpressed in HCCLM9 (7.31±0.73) versus MHCC97L (2.84±0.99), and validated by western blot and IHC from both nude mice tumor tissues and clinical specimens. Elevated coronin-1C expression was observed in liver cancer tissues of HCCLM9 nude mice. IHC study in 115 human HCC specimens demonstrated that patients with higher coronin-1C expession showed greater invasiveness and more advanced stage. Conclusion The study suggests coronin-1C could be a candidate biomarker to predict HCC invasive behavior.
Part One:Proteome analysis of serum from hepatocellular carcinoma model system with multiple metastatic potentials
Objective Serum proteomics approaches were applied to search for and validate hepatocellular carcinoma (HCC) invasion and metastasis related biomarkers. Methods 16 male athymic BALB/c nu/nu mice were randomly divided into two groups. HCCLM9-and MHCC97L-nude mice models of human HCC, with a similar genetic background and remarkably different pulmonary metastasis potential, were established.2D gel electrophoresis (2-DE) and MALDI-TOF/TOF technologies were used to construct a comparative proteome profile of nude mice sera from HCCLM9-and MHCC97L-nude mice. Candidate protein was confirmed by western blot and measured in sera from tumor development of spontaneous pulmonary metastasis in HCCLM9-nude mice. This result was further was analyzed by immunohistochemistry (IHC) on animal tumor tissues, and tissue micro-array on clinical specimens including 170 male cases and 38 female cases. Results Serum proteins from HCCLM9-and MHCC97L-nude mice were compared by 2-DE. A total of 11 proteins were identified by MALDI-TOF/TOF. Complement factor H (CFH) was overexpressed in HCCLM9-(213.83±55.17) versus MHCC97L-nude mice serum (122.48±48.91) by western blot, and validated by IHC from both nude mice tumor tissues and clinical specimens. Serum CFH level showed a remarkable upsurge when pulmonary metastasis occurred. Elevated CFH expression was observed in liver cancer tissues of HCCLM9 nude mice. IHC study in 208 human HCC specimens including demonstrated that patients with higher CFH expession showed greater invasiveness and more advanced stage. Conclusion The study suggests CFH could be a candidate biomarker to predict HCC invasive behavior.
引文
[1]Parkin DM, Bray F, Ferlay J. Global Cancer Statistics,2002. CA Cancer J Clin 2005; 55:74-108.
[2]Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD. A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130:187-196.
[3]Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation 1963; 1:174-180.
[4]Li D, Mallory T, Satomura S. Afp-13:a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001; 313:15-19.
[5]Weitz IC, Liebman HA. Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma:a critical review. Hepatology 1993; 18:990-997.
[6]Deugnier Y, David V, Brissot P, Mabo P, Delamaire D, Messner M. Serum alpha-1-fucosidase:a new marker for the diagnosis of primary hepatic carcinoma? Hepatology 1984; 4:889-892.
[7]Hsu HC, Cheng W, Lai PL. Cloning and Expression of a Developmentally Regulated Transcript MXR7 in Hepatocellular Carcinoma:Biological Significance and Temporospatial Distribution. Cancer Res 1997; 57:5179-5184.
[8]Ito N, Kawata S, Tamura S, Takaishi K, Shirai Y, Kiso S, Yabuuchi I, Matsuda Y, Nishioka M, Tarui S. Elevated levels of transforming growth factor beta messenger RNA and its polypeptide in human hepatocellular carcinoma. Cancer Res 1991; 51:4080-4083.
[9]Cariani E, Lasserre C, Seurin D, Hamelin B, Kemeny F, Franco D. Differential Expression of Insulin-like Growth Factor Ⅱ mRNA in Human Primary Liver Cancers, Benign Liver Tumors, and Liver Cirrhosis. Cancer Res 1988; 48:6844-6849.
[10]Ranke MB, Maier KP, Schweizer R, Stadler B, Schleicher S, Elmlinger MW. Pilot study of elevated levels of insulin-like growth factor-binding protein-2 as indicators of
hepatocellular carcinoma. Horm Res 2003; 60:174-180.
[11]Yoon SK, Lim NK, Ha SA, Park YG, Choi JY, Chung KW. The human cervical cancer oncogene protein is a biomarker for human hepatocellular carcinoma. Cancer Res 2004; 64:5434-5441.
[12]Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ. Gp73, a resident golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005; 43:1007-1012.
[13]Yamagamim H, Moriyama M, Matsumura H, Aoki H, Shimizu T, Saito T. Serum concentrations of human hepatocyte growth factor is a useful indicator for predicting the occurrence of hepatocellular carcinomas in c-viral chronic liver diseases. Cancer 2002; 95:824-834.
[14]Moriyama M, Matsumura H, Watanabe A, Nakamura H, Arakawa Y, Oshiro S. Detection of serum and intrahepatic KL-6 in anti-HCV positive patients with hepatocellular carcinoma. Hepatol Res 2004; 30:24-33.
[15]Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol 2004; 41:864-880.
[16]Hann HW, Lee J, Bussard A, Liu C, Jin YR, Guha K. Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma. Cancer Res 2004; 64:7329-7335.
[17]Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer 1999; 81:814-821.
[18]Li Y, Tang Y, Ye L, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 2001; 7:630-636.
[19]Li Y, Tang Y, Ye L, Liu B, Liu K, Chen J, Xue Q. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol 2003; 129:43-51.
[20]Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, Liu YK, Tang ZY. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol 2004; 130:460-468.
[21]伍龙,汤钊猷,李雁.肝癌模型的研究进展.中华实验外科杂志,2009；26：815-816.
[22]Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics 2004; 3:73-81.
[23]李雁,汤钊猷,田波,钦伦秀,叶胜龙,孙瑞霞.细胞角质蛋白19与肝癌临床病理关系的探讨.中华肝脏病杂志,2004;12：341-343.
[24]Matviw H, Yu G, Young D. Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins. Mol Cell Biol 1992; 12:5033-5040.
[25]Weitzdorfer R, Hoger H, Shim KS, Cekici L, Pollak A, Lubec G. Changes of hippocampal signaling protein levels during postnatal brain development in the rat. Hippocampus 2008; 18:807-813.
[26]Chaudhry F, Guerin C, von Witsch M, Blanchoin L, Staiger CJ. Identification of Arabidopsis cyclase-associated protein 1 as the first nucleotide exchange factor for plant actin. Mol Biol Cell 2007; 18:3002-3014.
[27]Frampton G, Moriya S, Pearson JD, Isenberg DA, Ward FJ, Smith TA, Panayiotou A, Staines NA, Murphy JJ. Identification of candidate endothelial cell autoantigens in systemic lupus erythematosus using a molecular cloning strategy:a role for ribosomal P protein P0 as an endothelial cell autoantigen. Rheumatology 2000; 39:1114-1120.
[28]Kinloch A, Tatzer V, Wait R, Peston D, Lundberg K, Donatien P, Moyes D, Taylor PC, Venables PJ. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res Ther 2005; 7:R1421-1429.
[29]Cauwe B, Martens E, Van den Steen PE, Proost P, Van Aelst I, Blockmans D, Opdenakker G. Adenylyl cyclase-associated protein-1/CAP 1 as a biological target substrate of gelatinase B/MMP-9. Exp Cell Res 2008; 314:2739-49.
[30]Han YH, Xia L, Song LP, Zheng Y, Chen WL, Zhang L, Huang Y, Chen GQ,Wang LS. Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells. Proteomics 2006; 6:3262-3274.
[31]Nakanishi H, Shindou H, Hishikawa D, Harayama T, Ogasawara R, Suwabe A, Taguchi R, Shimizu T. Cloning and characterization of mouse lung-type acyl-CoA: lysophosphatidylcholine acyltransferase 1 (LPCAT1):Expression in alveolar type II cells and possible involvement in surfactant production. J Biol Chem 2006; 281:20140-20147.
[32]Chen X, Hyatt BA, Mucenski ML, Mason RJ, Shannon JM. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc Natl Acad Sci U S A2006; 103:11724-11729.
[33]Agarwal AK, Sukumaran S, Bartz R, Barnes RI, Garg A. Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9:cloning, tissue distribution, gene structure, and enzymatic activity. J Endocrinol 2007; 193:445-457.
[34]Mansilla F, da Costa KA, Wang S, Kruh(?)ffer M, Lewin TM, Orntoft TF, Coleman RA, Birkenkamp-Demtroder K. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. J Mol Med 2009; 87:85-97.
[35]Creutz CE, Tomsig JL, Snyder SL, Gautier MC, Skouri F, Beisson J, Cohen J. The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans. J Biol Chem 1998; 273:1393-1402.
[36]Naslavsky N, Boehm M, Backlund PS Jr, Caplan S. Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Mol Biol Cell 2004; 15:2410-2422.
[37]George M, Ying G, Rainey MA, Solomon A, Parikh PT, Gao Q, Band V, Band H. Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans. BMC Cell Biol 2007; 8:3.
[38]Oosterhoff JK, Penninkhof F, Brinkmann AO, Grootegoed JA, Blok LJ. REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells. Oncogene 2003; 22:2920-2925.
[39]Jia J, Wang J, Teh M, Sun W, Zhang J, Kee I, Chow PK, Liang RC, Chung MC, Ge R. Identification of proteins differentially expressed between capillary endothelial cells of hepatocellular carcinoma and normal liver in an orthotopic rat tumor model using 2-D DIGE. Proteomics 2010; 10:224-234.
[40]Rapaport D, Auerbach W, Naslavsky N, Pasmanik-Chor M, Galperin E, Fein A, Caplan S, Joyner AL, Horowitz M. Recycling to the plasma membrane is delayed in EHD1 knockout mice. Traffic 2006; 10:52-60.
[41]Jovic M, Naslavsky N, Rapaport D, Horowitz M, Caplan S. EHD1 regulates beta 1 integrin endosomal transport:effects on focal adhesions, cell spreading and migration. J Cell Sci 2007; 120(Pt 5):802-814.
[42]Yasuda K, Nagafuku M, Shima T, Okada M, Yagi T, Yamada T, Minaki Y, Kato A, Tani-Ichi S, Hamaoka T, Kosugi A. Cutting edge:Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells. J Immunol 2002; 169:2813-2817.
[43]Weil R, Levraud JP, Dodon MD, Bessia C, Hazan U, Kourilsky P, Israel A. Altered expression of tyrosine kinases of the Src and Syk families in human T-cell leukemia virus type 1-infected T-cell lines. J Virol 1999; 73:3709-3717.
[44]Saad F. Src as a therapeutic target in men with prostate cancer and bone metastases. BJU Int 2009; 103:434-440.
[45]Chinni SR, Yamamoto H, Dong Z, Sabbota A, Bonfil RD, Cher ML. CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone. Mol Cancer Res 2008; 6:446-457.
[46]Haller F, Schulten HJ, Armbrust T, Langer C, Gunawan B, Fuzesi L. Multicentric sporadic gastrointestinal stromal tumors (GISTs) of the stomach with distinct clonal origin:differential diagnosis to familial and syndromal GIST variants and peritoneal metastasis. Am J Surg Pathol 2007; 31:933-937.
[47]Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, Sitia R. ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol
Chem 2000; 275:4827-4833.
[48]Benham AM, Cabibbo A, Fassio A, Bulleid N, Sitia R, Braakman I. The CXXCXXC motif determines the folding, structure and stability of human Erol-Lalpha. EMBO J 2000; 19:4493-4502.
[49]Mezghrani A, Fassio A, Benham A, Simmen T, Braakman I, Sitia R. Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J 2001; 20:6288-6296.
[50]Tsai B, Rapoport TA. Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Erol. J Cell Biol 2002; 159:207-216.
[51]Gess B, Hofbauer KH, Wenger RH, Lohaus C, Meyer HE, Kurtz A. The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-L alpha. Eur J Biochem 2003; 270:2228-2235.
[52]Salzer U, Kubicek M, Prohaska R. Isolation, molecular characterization, and tissue-specific expression of ECP-51 and ECP-54 (TIP49), two homologous, interacting erythroid cytosolic proteins. Biochim Biophys Acta 1999; 1446:365-370.
[53]Parfait B, Giovangrandi Y, Asheuer M, Laurendeau I, Olivi M, Vodovar N, Vidaud D, Vidaud M, Bieche I. Human TIP49b/RUVBL2 gene:genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3. Ann Genet 2000; 43:69-74.
[54]Kanemaki M, Kurokawa Y, Matsu-ura T, Makino Y, Masani A, Okazaki K, Morishita T, Tamura TA. TIP49b, a new RuvB-like DNA helicase, is included in a complex together with another RuvB-like DNA helicase, TIP49a. J Biol Chem 1999; 274:22437-2244.
[55]Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol 2004; 24:1884-1896.
[56]Xie X, Chen Y, Xue P, Fan Y, Deng Y, Peng G, Yang F, Xu T. RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation. Cell Res 2009; 19:1090-1097.
[57]Uetrecht AC, Bear JE. Coronins:the return of the crown. Trends Cell Biol 2006; 16:421-426.
[58]Rybakin V, Clemen CS. Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bioessays 2005; 27:625-632.
[59]Spoerl Z, Stumpf M, Noegel AA. Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus. J Biol Chem 2002; 277:48858-48867.
[60]Thal D, Xavier CP, Rosentreter A, Linder S, Friedrichs B, Waha A, Pietsch T, Stumpf M, Noegel A, Clemen C. Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol 2008; 214:415-424.
[61]Geisbrecht BV, Gould SJ. The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-dependent isocitrate dehydrogenase. J Biol Chem 1999; 274:30527-30533.
[62]Labussiere M, Sanson M, Idbaih A, Delattre JY. IDHl gene mutations:a new paradigm in glioma prognosis and therapy? Oncologist 2010; 15:196-199.
[63]Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321:1807-1812.
[64]Thompson CB. Metabolic enzymes as oncogenes or tumor suppressors. N Engl J Med 2009; 360:813-815.
[65]Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 Mutations in Gliomas. N Engl J Med 2009; 360:765-773.
[66]Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009; 27:4150-4154.
[67]Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, Ding J, Lei Q, Guan KL, Xiong Y. Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-la. Science 2009; 324:261-265.
[68]Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462:739-744.
[69]Yao DC, Tolan DR, Murray MF, Harris DJ, Darras BT, Geva A, Neufeld EJ. Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr. Blood 2004; 103:2401-2403.
[70]Esposito G, Vitagliano L, Costanzo P, Borrelli L, Barone R, Pavone L, Izzo P, Zagari A, Salvatore F. Human aldolase A natural mutants:relationship between flexibility of the C-terminal region and enzyme function. Biochem J 2004; 380(Pt 1):51-56.
[71]Yokoyama Y, Kuramitsu Y, Takashima M, Iizuka N, Toda T, Terai S, Sakaida I, Oka M, Nakamura K, Okita K. Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus. Proteomics.2004; 4:2111-2116.
[72]Munger JS, Shi GP, Mark EA, Chin DT, Gerard C. Chapman HAA serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. J Biol Chem 1991; 266:18832-18838.
[73]Morgan EW, Yan B, Greenway D, Petersen DR, Parkinson A. Purification and characterization of two rat liver microsomal carboxylesterases (hydrolase A and B). Arch Biochem Biophys 1994; 315:495-512.
[74]Cai L, Tang X, Guo L, An Y, Wang Y, Zheng J. Decreased serum levels of carboxylesterase-2 in patients with ovarian cancer. Tumori 2009; 95:473-478.
[75]Hori T, Hosokawa M. DNA methylation and its involvement in carboxylesterase 1A1 (CES1A1) gene expression. Xenobiotica 2010; 40:119-128.
[76]Christensen U, Simonsen M, Harrit N, Sottrup-Jensen L. Pregnancy zone protein, a proteinase-binding macroglobulin. Interactions with proteinases and methylamine. Biochemistry 1989; 28:9324-9331.
[77]Rodriguez D, Morrison CJ, Overall CM. Matrix metalloproteinases:What do they not do? New substrates and biological roles identified by murine models and proteomics. Biochim Biophys Acta 2010; 1803:39-54.
[78]Deryugina El, Quigley JP. Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis:Contrasting, overlapping and compensatory functions. Biochim Biophys Acta 2010; 1803:103-120.
[79]Kiernan UA, Nedelkov D, Tubbs KA, Niederkofler EE, Nelson RW. Proteomic characterization of novel serum amyloid P component variants from human plasma and urine. Proteomics 2004; 4:1825-1829.
[80]Mantzouranis EC, Dowton SB, Whitehead AS, Edge MD, Bruns GAP, Colten HR. Human serum amyloid P component. cDNA isolation, complete sequence of pre-serum amyloid P component, and localization of the gene to chromosome 1. J Biol Chem 1985; 260:7752-7756.
[81]Gazzana G, Borlak J. Mapping of the serum proteome of hepatocellular carcinoma induced by targeted overexpression of epidermal growth factor to liver cells of transgenic mice. J Proteome Res 2008; 7:928-937.
[82]Schaub NP, Jones KJ, Nyalwidhe JO, Cazares LH, Karbassi ID, Semmes OJ, Feliberti EC, Perry RR, Drake RR. Serum Proteomic Biomarker Discovery Reflective of Stage and Obesity in Breast Cancer Patients. J Am Coll Surg 2009; 208:970-978.
[83]Yi JK, Chang JW, Han W, Lee JW, Ko E, Kim DH, Bae JY, Yu J, Lee C, Yu MH, Noh DY Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein:A Novel Biomarker of Breast Cancer Screening and Diagnosis. Cancer Epidemiol Biomarkers Prev 2009; 18:1357-1364.
[84]Moon RT, McMahon AP. Generation of diversity in nonerythroid spectrins. Multiple polypeptides are predicted by sequence analysis of cDNAs encompassing the coding region of human nonerythroid alpha-spectrin. J Biol Chem 1990; 265:4427-4433.
[85]Yu MH, Im HG, Kim HI, Lee IS. Induction of Apoptosis by Immature Plum in Human Hepatocellular Carcinoma. J Med Food 2009; 12:518-527.
[86]Ying L, Katz Y, Schlesinger M, Carmi R, Shalev H, Haider N, Beck G, Sheffield VC, Landau D. Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 1999; 65:1538-1546.
[87]Jozsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol 2008; 29: 380-387.
[88]Jurianz K, Ziegler S, Garcia-Schiiler H. Complement resistance of tumor cells:basal and induced mechanisms. Mol Immunol 1999; 36:929-939.
[89]Gasque P, Julen N, Ischenko AM. Expression of complement components of the alternative pathway by glioma cell lines. J Immunol 1992; 149:1381-1387.
[90]Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer.2007; 7: 645-658.
[1]Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD. A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol.2004; 130(4):187-196.
[2]Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM. Experimental models of hepatocellular carcinoma. J Hepatol.2008; 48(5):858-79.
[3]Sell S. Mouse Models to Study the Interaction of Risk Factors for Human Liver Cancer. Cancer Res.2003; 63(22):7553-7562.
[4]Marx J. Medicine. Building better mouse models for studying cancer. Science.2003; 299(5615):1972-1975.
[5]McCoy GW. A preliminary report on tumors found in wild rats. J Med Res.1909; 21(2): 285-296.
[6]Frith CH, Wiley L. Spontaneous hepatocellular neoplasms and hepatic hemangiosarcomas in several strains of mice. Lab Anim Sci.1982; 32(2):157-62.
[7]Ratcliffe HL. Spontaneous tumors in two colonies of rats of the Wistar Institute of Anatomy and Biology. Amer J Path.1940; 16:237-254.
[8]Baenes JM, Schoental R. Experimental liver tumours. Br Med Bull.1958; 14(2):165-167.
[9]Kramer MG, Hernandez-Alcoceba R, Qian C, Prieto J. Evaluation of hepatocellular carcinoma models for preclinical studies. Drug Discov Today.2005; 2(1):41-49.
[10]Futakuchi M, Hirose M, Ogiso T, Kato K, Sano M, Ogawa K, Shirai T. Establishment of an in vivo highly metastatic rat hepatocellular carcinoma model. Jpn J Cancer Res 1999; 90(11):1196-202.
[11]Yoshino H, Futakuchi M, Cho YM, Ogawa K, Takeshita F, Imai N, Tamano S, Shirai T. Modification of an in vivo lung metastasis model of hepatocellular carcinomaby low dose N-nitrosomorpholine and diethylnitrosamine. Clin Exp Metastasis.2005; 22(5):441-447.
[12]Feo F, Pascale R, Calvisi D. Models for liver cancer. In:Alison M, editor. The cancer handbook. John Wiley & Sons; 2007,1-16.
[13]Cougot D, Neuveut C, Buendia MA. HBV induced carcinogenesis. J Clin Virol. 2005;34(1):S75-78.
[14]Dragani TA, Manenti G, Farza H, Della Porta G, Tiollais P, Pourcel C. Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis. Carcinogenesis.1990; 11(6):953-956.
[15]Singh M, Kumar V. Transgenic mouse models of hepatitis B virus-associated hepatocellular carcinoma. Rev Med Virol.2003:13(4):243-253.
[16]Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell.1989; 59(6):1145-1156.
[17]Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci U S A.1987; 84(19): 6909-6913.
[18]Koike K, Moriya K, Iino S, Yotsuyanagi H, Endo Y, Miyamura T, Kurokawa K. High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology.1994; 19(4):810-819.
[19]Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985; 230(4730):1157-1160.
[20]Toshkov I, Chisari FV, Bannasch P. Hepatic preneoplasia in hepatitis B virus transgenic mice. Hepatology.1994; 20(5):1162-1172.
[21]Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med.1998; 4(9):1065-1067.
[22]Koike K, Moriya K, Kimura S. Role of hepatitis C virus in the development of hepatocellular carcinoma:transgenic approach to viral hepatocarcinogenesis. J Gastroenterol Hepatol.2002; 17(4):394-400.
[23]Kamegaya Y, Hiasa Y, Zukerberg L, Fowler N, Blackard JT, Lin W, Choe WH, Schmidt EV, Chung RT. Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology.2005; 41(3):660-667.
[24]Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology.2002; 122(2): 352-365.
[25]Unoura M, Kobayashi K, Fukuoka K, Matsushita F, Morimoto H, Oshima T, Kaneko S, Hattori N, Murakami S, Yoshikawa H. Establishment of a cell line from a woodchuck hepatocellular carcinoma. Hepatology.1985; 5(6):1106-1111.
[26]Abe K, Kurata T, Yamada K, Okumura H, Shikata T. Establishment and characterization of a woodchuck hepatocellular carcinoma cell line (WH44KA). Jpn J Cancer Res.1988; 79(3):342-349.
[27]Lee H, Kawaguchi T, Nomura K, Kitagawa T. Establishment and characterization of a diethylnitrosamine-initiated woodchuck hepatocyte cell line. Hepatology.1987; 7(5): 937-940.
[28]Ohnishi S, Aoyama H, Shiga J, Itai Y, Moriyama T, Ishikawa T, Sasaki N, Yamamoto K, Koshimizu K, Kaneko S. Establishment of a new cell line from a woodchuck hepatocellular carcinoma. Hepatology.1988; 8(1):104-107.
[29]Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985; 230(4730):1157-1160.
[30]Babinet C, Farza H, Morello D, Hadchouel M, Pourcel C. Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. Science.1985; 230(4730):1160-1163.
[31]Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell.1989; 59(6):1145-1156.
[32]Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature.1991; 351(6324):317-320.
[33]Koike K. Hepatitis B virus HBx gene and hepatocarcinogenesis. Intervirology.1995; 38(3-4):134-142.
[34]Milich DR, Jones JE, Hughes JL, Maruyama T, Price J, Melhado I, Jirik F. Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice. J Immunol.1994; 152(2):455-466.
[35]Wang Y, Cui F, Lv Y, Li C, Xu X, Deng C, Wang D, Sun Y, Hu G, Lang Z, Huang C, Yang X. HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology.2004; 39(2):318-324.
[36]Park US, Su JJ, Ban KC, Qin L, Lee EH, Lee YI. Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin Bl. Gene.2000; 251(1):73-80.
[37]Dunsford HA, Sell S, Chisari FV. Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res.1990;50(11):3400-3407.
[38]Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS. Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. Mol Carcinog.1996; 15(4):261-269.
[39]Yu DY, Moon HB, Son JK, Jeong S, Yu SL, Yoon H, Han YM, Lee CS, Park JS, Lee CH, Hyun BH, Murakami S, Lee KK. Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein. J Hepatol.1999; 31(1):123-132.
[40]Lee TH, Finegold MJ, Shen RF, DeMayo J L, Woo SL, Butel JS. Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J Virol.1990; 64(12): 5939-5947.
[41]Zheng Y, Chen WL, Louie SG, Yen TS, Ou JH. Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice. Hepatology.2007; 45(1):16-21.
[42]Barone M, Leo DA, Maiorano E, Panella E, Scavo MP, Castellaneta A, Francavilla D, Francioso A. Role of sex steroid hormones on hepatocellular carcinoma (HCC) development in HBV transgenic mice. Dig Liver Dis.2007; 39(3):A23-24.
[43]Levrero M. Viral hepatitis and liver cancer:the case of hepatitis C. Oncogene.2006; 25(27):3834-3847.
[44]Ray RB, Lagging LM, Meyer K, Ray R. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol. 1996; 70(7):4438-4443.
[45]Ray RB, Meyer K, Ray R. Suppression of apoptotic cell death by hepatitis C virus core protein. Virology.1996; 226(2):176-182.
[46]McLauchlan J. Properties of the hepatitis C virus core protein:a structural protein that modulates cellular processes. J Viral Hepat.2000; 7(1):2-14.
[47]Tellinghuisen TL, Rice CM. Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol.2002; 5(4):419-427.
[48]Tanaka N, Moriya K, Kiyosawa K, Koike K, Aoyama T. Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice:implications for HCV-associated hepatocarcinogenesis. Int J Cancer.2008; 122(1):124-131.
[49]Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B. Infectious agents and cancer:criteria for a causal relation. Semin Cancer Biol.2004; 14(6):453-471.
[50]Jacob JR, Sterczer A, Toshkov IA. Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors. Hepatology.2004; 39(4):1008-1016.
[51]Knowles BB, Howe CC, Aden DP, Yeager AE, Korba BE, Cote PJ, Buendia MA, Gerin JL, Tennant BC. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science.1980; 209(4455):497-499.
[52]Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature.1979:282(5739): 615-616.
[53]Busch SJ, Barnhart RL, Martin GA, Flanagan MA, Jackson RL. Differential regulation of hepatic triglyceride lipase and 3-hydroxy-3-methylglutaryl-CoA reductase gene expression in a human hepatoma cell line, HepG2. J Biol Chem.1990; 265(36): 22474-22479.
[54]Zannis VI, Breslow JL, SanGiacomo TR, Aden DP, Knowles BB. Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. Biochemistry.1981; 20(25):7089-7096.
[55]Jiao W, Miyazaki K, Kitajima Y. Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer.2002; 86(1):98-101.
[56]Takahashi M, Sato T, Sagawa T, Lu Y, Sato Y, Iyama S, Yamada Y, Fukaura J, Takahashi S, Miyanishi K, Yamashita T, Sasaki K, Kogawa K, Hamada H, Kato J, Niitsu Y, et al. E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor. Mol Ther.2002; 5(5 Pt 1):627-634.
[57]Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst.1977; 59(1):221-226.
[58]Heffelfinger SC, Hawkins HH, Barrish J, Taylor L, Darlington GJ. SK HEP-1:a human cell line of endothelial origin. In Vitro Cell Dev Biol.1992; 28A(2):136-142.
[59]Yan J, Yu Y, Wang N, Chang Y, Ying H, Liu W, He J, Li S, Jiang W, Li Y, Liu H, Wang H, Xu Y. LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. Oncogene.2004; 23(10): 1939-1949.
[60]Wang XW, Yuan JH, Zhang RG, Guo LX, Xie Y, Xie H. Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice. World J Gastroenterol.2001; 7(3):345-351.
[61]Monjardino J, Crawford E. Polypeptide profile of HBSAg excreted by a human hepatoma cell line. Virology.1979; 96(2):652-655.
[62]MacNab GM, Alexander JJ, Lecatsas G, Bey EM, Urbanowicz JM. Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer.1976; 34(5):509-515.
[63]Skelly J, Copeland JA, Howard CR, Zuckerman AJ. Hepatitis B surface antigen produced by a human hepatoma cell line. Nature.1979; 282(5739):617-618.
[64]Ling CQ, Li B, Zhang C, Zhu DZ, Huang XQ, Gu W, Li SX. Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann Oncol. 2005; 16(1):109-115.
[65]Li B, Gu W, Zhang C, Han KQ, Ling CQ. Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie.2006; 29(8-9):367-371.
[66]Park JG, Lee JH, Kang MS, Park KJ, Jeon YM, Lee HJ, Kwon HS, Park HS, Yeo KS, Lee KU. Characterization of cell lines established from human hepatocellular carcinoma. Int J Cancer.1995; 62(3):276-282
[67]Lee JH, Ku JL, Park YJ, Lee KU, Kim WH, Park JG. Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. World J Gastroenterol.1999; 5(4):289-295.
[68]Lou CY, Feng YM, Qian AR, Li Y, Tang H, Shang P, Chen ZN. Establishment and characterization of human hepatocellular carcinoma cell line FHCC-98. World J Gastroenterol.2004; 10(10):1462-1465.
[69]Wen JM, Huang JF, Hu L, Wang WS, Zhang M, Sham JS, Xu JM, Zeng WF, Xie D, Liang LJ, Guan XY. Establishment and characterization of human metastatic hepatocellular carcinoma cell line. Cancer Genet Cytogenet.2002; 135(1):91-95.
[70]Armengol C, Tarafa G, Boix L, Sole M, Queralt R, Costa D, Bachs O, Bruix J, Capella G. Orthotopic implantation of human hepatocellular carcinoma in mice:analysis of tumor progression and establishment of the BCLC-9 cell line. Clin Cancer Res.2004; 10(6): 2150-2157.
[71]Sun FX, Tang ZY, Liu KD, Xue Q, Gao DM, Yu YQ, Zhou XD, Ma ZC. Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens. J Cancer Res Clin Oncol.1996; 122(7):397-402.
[72]Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer.1999; 81(5):814-821.
[73]Li Y, Tang Y, Ye L, Liu B, Liu K, Chen J, Xue Q. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol.2003; 129(1):43-51.
[74]Li Y, Tang Y, Ye L, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol.2001:7(5):630-636.
[75]Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, Liu YK, Tang ZY. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol.2004; 130(8):460-468.
[76]Darlington GJ, Bernhard HP, Miller RA, Ruddle FH. Expression of liver phenotypes in cultured mouse hepatoma cells. J Natl Cancer Inst.1980; 64(4):809-819.
[77]Tatsumi T, Takehara T, Kanto T, Miyagi T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N. Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. Cancer Res.2001; 61(20):7563-7567.
[78]Yamashita YI, Shimada M, Hasegawa H, Minagawa R, Rikimaru T, Hamatsu T, Tanaka S, Shirabe K, Miyazaki JI, Sugimachi K. Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res.2001; 61(3): 1005-1012.
[79]Morris HP, Meranze DR. Induction and some characteristics of "Minimal Deviation" and other transplantable rat hepatomas. Recent Results Cancer Res.1974; 44:103-114.
[80]Kulas DT, Goldstein BJ, Mooney RA. The transmembrane protein-tyrosine phosphatase LAR modulates signaling by multiple receptor tyrosine kinases. J Biol Chem.1996; 271(2):748-754.
[81]Schock D, Kuo SR, Steinburg MF, Bolognino M, Sparks JD, Sparks CE, Smith HC. An auxiliary factor containing a 240-kDa protein complex is involved in apolipoprotein B RNA editing. Proc Natl Acad Sci U S A.1996; 93(3):1097-1102.
[82]Ryall J, Rachubinski RA, Nguyen M, Rozen R, Broglie KE, Shore GC. Regulation and expression of carbamyl phosphate synthetase I mRNA in developing rat liver and Morris hepatoma 5123D. J Biol Chem.1984; 259(14):9172-9176.
[83]Calviello G, Palozza P, Piccioni E, Maggiano N, Frattucci A, Franceschelli P, Bartoli GM. Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats:effects on proliferation and apoptosis. Int J Cancer.1998; 75(5):699-705.
[84]Barnard GF, Erickson SK, Cooper AD. Regulation of lipoprotein receptors on rat hepatomas in vivo. Biochim Biophys Acta.1986; 879(3):301-312.
[85]Benedict WF, Gielen JE, Owens IS, Niwa A, Bebert DW. Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. IV. Stimulation of the enzyme activity in established cell lines derived from rat or mouse hepatoma and from normal rat liver. Biochem Pharmacol.1973; 22(21):2766-2769.
[86]Sassier P, Bergeron M. Specific inhibition of cell proliferation in the mouse intestine by an aqueous extract of rabbit small intestine. Cell Tissue Kinet.1977; 10(3):223-231.
[87]Bradlaw JA, Casterline JL Jr. Induction of enzyme activity in cell culture:a rapid screen for detection of planar polychlorinated organic compounds. J Assoc Off Anal Chem.1979; 62(4):904-916.
[88]Haggerty DF, Young PL, Popjak G, Carnes WH. Phenylalanine hydroxylase in cultured hepatoxytes. I. Hormonal control of enzyme levels. J Biol Chem.1973; 248(1):223-232.
[89]Carb6 N, Lopez-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, Quinn LS, Lopez-Soriano FJ, Argiles JM. Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br J Cancer.2000; 83(4):526-531.
[90]Lin SB, Wu LC, Huang SL, Hsu HL, Hsieh SH, Chi CW, Au LC. In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha. J Hepatol.2000; 33(4):601-608.
[91]Ogawa K, Nakanishi H, Takeshita F. Establishment of rat hepatocellular carcinoma cell lines with differing metastatic potential in nude mice. Int J Cancer.2001; 91(6):797-802.
[92]Novicki DL, Jirtle RL, Michalopoulos G. Establishment of two rat hepatoma cell strains produced by a carcinogen initiation, phenobarbital promotion protocol. In Vitro.1983; 19(3 Pt 1):191-202.
[93]Li HF, Ling MY, Xie Y, Xie H. Establishment of a lymph node metastatic model of mouse hepatocellular carcinoma Hca-F cells in C3H/Hej mice. Oncol Res.1998; 10(11-12):569-573.
[94]Cespedes MV, Casanova I, Parreno M, Mangues R. Mouse models in oncogenesis and cancer therapy. Clin Transl Oncol.2006; 8(5):318-329.
[95]Killion JJ, Radinsky R, Fidler IJ. Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metastasis Rev.1998-1999; 17(3):279-284.
[96]Kerbel RS. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans:better than commonly perceived-but they can be improved. Cancer Biol Ther.2003; 2(4 Suppl 1):S134-139.
[97]Hoffman RM. Orthotopic metastatic mouse models for anticancer drug discovery and evaluation:a bridge to the clinic. Invest New Drugs.1999;17(4):343-359.
[98]Hoffman RM. Orthotopic metastatic (MetaMouse) models for discovery and development of novel chemotherapy. Methods Mol Med.2005; 111:297-322.
[99]Li Y, Tang ZY, Tian B, Ye SL, Qin LX, Xue Q, Sun RX. Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis:study in nude mice model and clinical patients. J Cancer Res Clin Oncol.2006; 132(8):515-520.
[100]Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics.2004; 3(1):73-81.
[101]Albini A. Tumor microenvironment, a dangerous society leading to cancer metastasis. From mechanisms to therapy and prevention. Cancer Metastasis Rev.2008; 27(1):3-4.
[102]Ji XN, Ye SL, Li Y, Tian B, Chen J, Gao DM, Chen J, Bao WH, Liu YK, Tang ZY. Contributions of lung tissue extracts to invasion and migration of human hepatocellular carcinoma cells with various metastatic potentials. J Cancer Res Clin Oncol.2003; 129(10):556-564.
[103]Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer.2007; 7(9):645-658.
[104]Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature.2001; 414(6859):105-111.
[105]Alison MR, Lovell MJ. Liver cancer:the role of stem cells. Cell Prolif.2005; 38(6): 407-421.
[106]Sell S, Leffert HL. Liver cancer stem cells. J Clin Oncol.2008; 26(17):2800-2805.
[107]Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene.2008; 27(12):1749-1758.
[108]Talmadge JE, Singh RK, Fidler IJ, Raz A. Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol.2007; 170(3):793-804.
[109]Tamano S, Merlino GT, Ward JM. Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. Carcinogenesis.1994; 15(9):1791-1798.
[110]Liu G, McDonnell TJ, Montes de Oca Luna R, Kapoor M, Mims B, El-Naggar AK, Lozano G. High metastatic potential in mice inheriting a targeted p53 missense mutation. Proc Natl Acad Sci U S A.2000; 97(8):4174-4179.
[111]Neumann CA, Krause DS, Carman CV. Essential role for the peroxiredoxin Prdxl in erythrocyte antioxidant defence and tumour suppression. Nature.2003; 424(6948): 561-565.
[112]Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS. Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. Am J Pathol.1996; 149(2):407-428.
[113]Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest.2004; 113(12):1774-1783.
[114]Damo LA, Snyder PW, Franklin DS. Tumorigenesis in p27/p53-and pl8/p53-double null mice:functional collaboration between the pRb and p53 pathways. Mol Carcinog. 2005; 42(2):109-120.
[115]Cheo DL, Burns DK, Meira LB, Houle JF, Friedberg EC. Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/-mice. Cancer Res.1999; 59(4):771-775.
[116]D Dubois N, Bennoun M, Allemand I, Molina T, Grimber G, Daudet-Monsac M, Abelanet R, Briand P. Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J Hepatol.1991; 13(2):227-239.
[2]Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD. A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130:187-196.
[3]Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation 1963; 1:174-180.
[4]Li D, Mallory T, Satomura S. Afp-13:a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001; 313:15-19.
[5]Weitz IC, Liebman HA. Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma:a critical review. Hepatology 1993; 18:990-997.
[6]Deugnier Y, David V, Brissot P, Mabo P, Delamaire D, Messner M. Serum alpha-1-fucosidase:a new marker for the diagnosis of primary hepatic carcinoma? Hepatology 1984; 4:889-892.
[7]Hsu HC, Cheng W, Lai PL. Cloning and Expression of a Developmentally Regulated Transcript MXR7 in Hepatocellular Carcinoma:Biological Significance and Temporospatial Distribution. Cancer Res 1997; 57:5179-5184.
[8]Ito N, Kawata S, Tamura S, Takaishi K, Shirai Y, Kiso S, Yabuuchi I, Matsuda Y, Nishioka M, Tarui S. Elevated levels of transforming growth factor beta messenger RNA and its polypeptide in human hepatocellular carcinoma. Cancer Res 1991; 51:4080-4083.
[9]Cariani E, Lasserre C, Seurin D, Hamelin B, Kemeny F, Franco D. Differential Expression of Insulin-like Growth Factor Ⅱ mRNA in Human Primary Liver Cancers, Benign Liver Tumors, and Liver Cirrhosis. Cancer Res 1988; 48:6844-6849.
[10]Ranke MB, Maier KP, Schweizer R, Stadler B, Schleicher S, Elmlinger MW. Pilot study of elevated levels of insulin-like growth factor-binding protein-2 as indicators of
hepatocellular carcinoma. Horm Res 2003; 60:174-180.
[11]Yoon SK, Lim NK, Ha SA, Park YG, Choi JY, Chung KW. The human cervical cancer oncogene protein is a biomarker for human hepatocellular carcinoma. Cancer Res 2004; 64:5434-5441.
[12]Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ. Gp73, a resident golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005; 43:1007-1012.
[13]Yamagamim H, Moriyama M, Matsumura H, Aoki H, Shimizu T, Saito T. Serum concentrations of human hepatocyte growth factor is a useful indicator for predicting the occurrence of hepatocellular carcinomas in c-viral chronic liver diseases. Cancer 2002; 95:824-834.
[14]Moriyama M, Matsumura H, Watanabe A, Nakamura H, Arakawa Y, Oshiro S. Detection of serum and intrahepatic KL-6 in anti-HCV positive patients with hepatocellular carcinoma. Hepatol Res 2004; 30:24-33.
[15]Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol 2004; 41:864-880.
[16]Hann HW, Lee J, Bussard A, Liu C, Jin YR, Guha K. Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma. Cancer Res 2004; 64:7329-7335.
[17]Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer 1999; 81:814-821.
[18]Li Y, Tang Y, Ye L, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 2001; 7:630-636.
[19]Li Y, Tang Y, Ye L, Liu B, Liu K, Chen J, Xue Q. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol 2003; 129:43-51.
[20]Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, Liu YK, Tang ZY. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol 2004; 130:460-468.
[21]伍龙,汤钊猷,李雁.肝癌模型的研究进展.中华实验外科杂志,2009；26：815-816.
[22]Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics 2004; 3:73-81.
[23]李雁,汤钊猷,田波,钦伦秀,叶胜龙,孙瑞霞.细胞角质蛋白19与肝癌临床病理关系的探讨.中华肝脏病杂志,2004;12：341-343.
[24]Matviw H, Yu G, Young D. Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins. Mol Cell Biol 1992; 12:5033-5040.
[25]Weitzdorfer R, Hoger H, Shim KS, Cekici L, Pollak A, Lubec G. Changes of hippocampal signaling protein levels during postnatal brain development in the rat. Hippocampus 2008; 18:807-813.
[26]Chaudhry F, Guerin C, von Witsch M, Blanchoin L, Staiger CJ. Identification of Arabidopsis cyclase-associated protein 1 as the first nucleotide exchange factor for plant actin. Mol Biol Cell 2007; 18:3002-3014.
[27]Frampton G, Moriya S, Pearson JD, Isenberg DA, Ward FJ, Smith TA, Panayiotou A, Staines NA, Murphy JJ. Identification of candidate endothelial cell autoantigens in systemic lupus erythematosus using a molecular cloning strategy:a role for ribosomal P protein P0 as an endothelial cell autoantigen. Rheumatology 2000; 39:1114-1120.
[28]Kinloch A, Tatzer V, Wait R, Peston D, Lundberg K, Donatien P, Moyes D, Taylor PC, Venables PJ. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res Ther 2005; 7:R1421-1429.
[29]Cauwe B, Martens E, Van den Steen PE, Proost P, Van Aelst I, Blockmans D, Opdenakker G. Adenylyl cyclase-associated protein-1/CAP 1 as a biological target substrate of gelatinase B/MMP-9. Exp Cell Res 2008; 314:2739-49.
[30]Han YH, Xia L, Song LP, Zheng Y, Chen WL, Zhang L, Huang Y, Chen GQ,Wang LS. Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells. Proteomics 2006; 6:3262-3274.
[31]Nakanishi H, Shindou H, Hishikawa D, Harayama T, Ogasawara R, Suwabe A, Taguchi R, Shimizu T. Cloning and characterization of mouse lung-type acyl-CoA: lysophosphatidylcholine acyltransferase 1 (LPCAT1):Expression in alveolar type II cells and possible involvement in surfactant production. J Biol Chem 2006; 281:20140-20147.
[32]Chen X, Hyatt BA, Mucenski ML, Mason RJ, Shannon JM. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc Natl Acad Sci U S A2006; 103:11724-11729.
[33]Agarwal AK, Sukumaran S, Bartz R, Barnes RI, Garg A. Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9:cloning, tissue distribution, gene structure, and enzymatic activity. J Endocrinol 2007; 193:445-457.
[34]Mansilla F, da Costa KA, Wang S, Kruh(?)ffer M, Lewin TM, Orntoft TF, Coleman RA, Birkenkamp-Demtroder K. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. J Mol Med 2009; 87:85-97.
[35]Creutz CE, Tomsig JL, Snyder SL, Gautier MC, Skouri F, Beisson J, Cohen J. The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans. J Biol Chem 1998; 273:1393-1402.
[36]Naslavsky N, Boehm M, Backlund PS Jr, Caplan S. Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Mol Biol Cell 2004; 15:2410-2422.
[37]George M, Ying G, Rainey MA, Solomon A, Parikh PT, Gao Q, Band V, Band H. Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans. BMC Cell Biol 2007; 8:3.
[38]Oosterhoff JK, Penninkhof F, Brinkmann AO, Grootegoed JA, Blok LJ. REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells. Oncogene 2003; 22:2920-2925.
[39]Jia J, Wang J, Teh M, Sun W, Zhang J, Kee I, Chow PK, Liang RC, Chung MC, Ge R. Identification of proteins differentially expressed between capillary endothelial cells of hepatocellular carcinoma and normal liver in an orthotopic rat tumor model using 2-D DIGE. Proteomics 2010; 10:224-234.
[40]Rapaport D, Auerbach W, Naslavsky N, Pasmanik-Chor M, Galperin E, Fein A, Caplan S, Joyner AL, Horowitz M. Recycling to the plasma membrane is delayed in EHD1 knockout mice. Traffic 2006; 10:52-60.
[41]Jovic M, Naslavsky N, Rapaport D, Horowitz M, Caplan S. EHD1 regulates beta 1 integrin endosomal transport:effects on focal adhesions, cell spreading and migration. J Cell Sci 2007; 120(Pt 5):802-814.
[42]Yasuda K, Nagafuku M, Shima T, Okada M, Yagi T, Yamada T, Minaki Y, Kato A, Tani-Ichi S, Hamaoka T, Kosugi A. Cutting edge:Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells. J Immunol 2002; 169:2813-2817.
[43]Weil R, Levraud JP, Dodon MD, Bessia C, Hazan U, Kourilsky P, Israel A. Altered expression of tyrosine kinases of the Src and Syk families in human T-cell leukemia virus type 1-infected T-cell lines. J Virol 1999; 73:3709-3717.
[44]Saad F. Src as a therapeutic target in men with prostate cancer and bone metastases. BJU Int 2009; 103:434-440.
[45]Chinni SR, Yamamoto H, Dong Z, Sabbota A, Bonfil RD, Cher ML. CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone. Mol Cancer Res 2008; 6:446-457.
[46]Haller F, Schulten HJ, Armbrust T, Langer C, Gunawan B, Fuzesi L. Multicentric sporadic gastrointestinal stromal tumors (GISTs) of the stomach with distinct clonal origin:differential diagnosis to familial and syndromal GIST variants and peritoneal metastasis. Am J Surg Pathol 2007; 31:933-937.
[47]Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, Sitia R. ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol
Chem 2000; 275:4827-4833.
[48]Benham AM, Cabibbo A, Fassio A, Bulleid N, Sitia R, Braakman I. The CXXCXXC motif determines the folding, structure and stability of human Erol-Lalpha. EMBO J 2000; 19:4493-4502.
[49]Mezghrani A, Fassio A, Benham A, Simmen T, Braakman I, Sitia R. Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J 2001; 20:6288-6296.
[50]Tsai B, Rapoport TA. Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Erol. J Cell Biol 2002; 159:207-216.
[51]Gess B, Hofbauer KH, Wenger RH, Lohaus C, Meyer HE, Kurtz A. The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-L alpha. Eur J Biochem 2003; 270:2228-2235.
[52]Salzer U, Kubicek M, Prohaska R. Isolation, molecular characterization, and tissue-specific expression of ECP-51 and ECP-54 (TIP49), two homologous, interacting erythroid cytosolic proteins. Biochim Biophys Acta 1999; 1446:365-370.
[53]Parfait B, Giovangrandi Y, Asheuer M, Laurendeau I, Olivi M, Vodovar N, Vidaud D, Vidaud M, Bieche I. Human TIP49b/RUVBL2 gene:genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3. Ann Genet 2000; 43:69-74.
[54]Kanemaki M, Kurokawa Y, Matsu-ura T, Makino Y, Masani A, Okazaki K, Morishita T, Tamura TA. TIP49b, a new RuvB-like DNA helicase, is included in a complex together with another RuvB-like DNA helicase, TIP49a. J Biol Chem 1999; 274:22437-2244.
[55]Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol 2004; 24:1884-1896.
[56]Xie X, Chen Y, Xue P, Fan Y, Deng Y, Peng G, Yang F, Xu T. RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation. Cell Res 2009; 19:1090-1097.
[57]Uetrecht AC, Bear JE. Coronins:the return of the crown. Trends Cell Biol 2006; 16:421-426.
[58]Rybakin V, Clemen CS. Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bioessays 2005; 27:625-632.
[59]Spoerl Z, Stumpf M, Noegel AA. Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus. J Biol Chem 2002; 277:48858-48867.
[60]Thal D, Xavier CP, Rosentreter A, Linder S, Friedrichs B, Waha A, Pietsch T, Stumpf M, Noegel A, Clemen C. Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol 2008; 214:415-424.
[61]Geisbrecht BV, Gould SJ. The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-dependent isocitrate dehydrogenase. J Biol Chem 1999; 274:30527-30533.
[62]Labussiere M, Sanson M, Idbaih A, Delattre JY. IDHl gene mutations:a new paradigm in glioma prognosis and therapy? Oncologist 2010; 15:196-199.
[63]Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321:1807-1812.
[64]Thompson CB. Metabolic enzymes as oncogenes or tumor suppressors. N Engl J Med 2009; 360:813-815.
[65]Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 Mutations in Gliomas. N Engl J Med 2009; 360:765-773.
[66]Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009; 27:4150-4154.
[67]Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, Ding J, Lei Q, Guan KL, Xiong Y. Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-la. Science 2009; 324:261-265.
[68]Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462:739-744.
[69]Yao DC, Tolan DR, Murray MF, Harris DJ, Darras BT, Geva A, Neufeld EJ. Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr. Blood 2004; 103:2401-2403.
[70]Esposito G, Vitagliano L, Costanzo P, Borrelli L, Barone R, Pavone L, Izzo P, Zagari A, Salvatore F. Human aldolase A natural mutants:relationship between flexibility of the C-terminal region and enzyme function. Biochem J 2004; 380(Pt 1):51-56.
[71]Yokoyama Y, Kuramitsu Y, Takashima M, Iizuka N, Toda T, Terai S, Sakaida I, Oka M, Nakamura K, Okita K. Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus. Proteomics.2004; 4:2111-2116.
[72]Munger JS, Shi GP, Mark EA, Chin DT, Gerard C. Chapman HAA serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. J Biol Chem 1991; 266:18832-18838.
[73]Morgan EW, Yan B, Greenway D, Petersen DR, Parkinson A. Purification and characterization of two rat liver microsomal carboxylesterases (hydrolase A and B). Arch Biochem Biophys 1994; 315:495-512.
[74]Cai L, Tang X, Guo L, An Y, Wang Y, Zheng J. Decreased serum levels of carboxylesterase-2 in patients with ovarian cancer. Tumori 2009; 95:473-478.
[75]Hori T, Hosokawa M. DNA methylation and its involvement in carboxylesterase 1A1 (CES1A1) gene expression. Xenobiotica 2010; 40:119-128.
[76]Christensen U, Simonsen M, Harrit N, Sottrup-Jensen L. Pregnancy zone protein, a proteinase-binding macroglobulin. Interactions with proteinases and methylamine. Biochemistry 1989; 28:9324-9331.
[77]Rodriguez D, Morrison CJ, Overall CM. Matrix metalloproteinases:What do they not do? New substrates and biological roles identified by murine models and proteomics. Biochim Biophys Acta 2010; 1803:39-54.
[78]Deryugina El, Quigley JP. Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis:Contrasting, overlapping and compensatory functions. Biochim Biophys Acta 2010; 1803:103-120.
[79]Kiernan UA, Nedelkov D, Tubbs KA, Niederkofler EE, Nelson RW. Proteomic characterization of novel serum amyloid P component variants from human plasma and urine. Proteomics 2004; 4:1825-1829.
[80]Mantzouranis EC, Dowton SB, Whitehead AS, Edge MD, Bruns GAP, Colten HR. Human serum amyloid P component. cDNA isolation, complete sequence of pre-serum amyloid P component, and localization of the gene to chromosome 1. J Biol Chem 1985; 260:7752-7756.
[81]Gazzana G, Borlak J. Mapping of the serum proteome of hepatocellular carcinoma induced by targeted overexpression of epidermal growth factor to liver cells of transgenic mice. J Proteome Res 2008; 7:928-937.
[82]Schaub NP, Jones KJ, Nyalwidhe JO, Cazares LH, Karbassi ID, Semmes OJ, Feliberti EC, Perry RR, Drake RR. Serum Proteomic Biomarker Discovery Reflective of Stage and Obesity in Breast Cancer Patients. J Am Coll Surg 2009; 208:970-978.
[83]Yi JK, Chang JW, Han W, Lee JW, Ko E, Kim DH, Bae JY, Yu J, Lee C, Yu MH, Noh DY Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein:A Novel Biomarker of Breast Cancer Screening and Diagnosis. Cancer Epidemiol Biomarkers Prev 2009; 18:1357-1364.
[84]Moon RT, McMahon AP. Generation of diversity in nonerythroid spectrins. Multiple polypeptides are predicted by sequence analysis of cDNAs encompassing the coding region of human nonerythroid alpha-spectrin. J Biol Chem 1990; 265:4427-4433.
[85]Yu MH, Im HG, Kim HI, Lee IS. Induction of Apoptosis by Immature Plum in Human Hepatocellular Carcinoma. J Med Food 2009; 12:518-527.
[86]Ying L, Katz Y, Schlesinger M, Carmi R, Shalev H, Haider N, Beck G, Sheffield VC, Landau D. Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 1999; 65:1538-1546.
[87]Jozsi M, Zipfel PF. Factor H family proteins and human diseases. Trends Immunol 2008; 29: 380-387.
[88]Jurianz K, Ziegler S, Garcia-Schiiler H. Complement resistance of tumor cells:basal and induced mechanisms. Mol Immunol 1999; 36:929-939.
[89]Gasque P, Julen N, Ischenko AM. Expression of complement components of the alternative pathway by glioma cell lines. J Immunol 1992; 149:1381-1387.
[90]Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer.2007; 7: 645-658.
[1]Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD. A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol.2004; 130(4):187-196.
[2]Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM. Experimental models of hepatocellular carcinoma. J Hepatol.2008; 48(5):858-79.
[3]Sell S. Mouse Models to Study the Interaction of Risk Factors for Human Liver Cancer. Cancer Res.2003; 63(22):7553-7562.
[4]Marx J. Medicine. Building better mouse models for studying cancer. Science.2003; 299(5615):1972-1975.
[5]McCoy GW. A preliminary report on tumors found in wild rats. J Med Res.1909; 21(2): 285-296.
[6]Frith CH, Wiley L. Spontaneous hepatocellular neoplasms and hepatic hemangiosarcomas in several strains of mice. Lab Anim Sci.1982; 32(2):157-62.
[7]Ratcliffe HL. Spontaneous tumors in two colonies of rats of the Wistar Institute of Anatomy and Biology. Amer J Path.1940; 16:237-254.
[8]Baenes JM, Schoental R. Experimental liver tumours. Br Med Bull.1958; 14(2):165-167.
[9]Kramer MG, Hernandez-Alcoceba R, Qian C, Prieto J. Evaluation of hepatocellular carcinoma models for preclinical studies. Drug Discov Today.2005; 2(1):41-49.
[10]Futakuchi M, Hirose M, Ogiso T, Kato K, Sano M, Ogawa K, Shirai T. Establishment of an in vivo highly metastatic rat hepatocellular carcinoma model. Jpn J Cancer Res 1999; 90(11):1196-202.
[11]Yoshino H, Futakuchi M, Cho YM, Ogawa K, Takeshita F, Imai N, Tamano S, Shirai T. Modification of an in vivo lung metastasis model of hepatocellular carcinomaby low dose N-nitrosomorpholine and diethylnitrosamine. Clin Exp Metastasis.2005; 22(5):441-447.
[12]Feo F, Pascale R, Calvisi D. Models for liver cancer. In:Alison M, editor. The cancer handbook. John Wiley & Sons; 2007,1-16.
[13]Cougot D, Neuveut C, Buendia MA. HBV induced carcinogenesis. J Clin Virol. 2005;34(1):S75-78.
[14]Dragani TA, Manenti G, Farza H, Della Porta G, Tiollais P, Pourcel C. Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis. Carcinogenesis.1990; 11(6):953-956.
[15]Singh M, Kumar V. Transgenic mouse models of hepatitis B virus-associated hepatocellular carcinoma. Rev Med Virol.2003:13(4):243-253.
[16]Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell.1989; 59(6):1145-1156.
[17]Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci U S A.1987; 84(19): 6909-6913.
[18]Koike K, Moriya K, Iino S, Yotsuyanagi H, Endo Y, Miyamura T, Kurokawa K. High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology.1994; 19(4):810-819.
[19]Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985; 230(4730):1157-1160.
[20]Toshkov I, Chisari FV, Bannasch P. Hepatic preneoplasia in hepatitis B virus transgenic mice. Hepatology.1994; 20(5):1162-1172.
[21]Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med.1998; 4(9):1065-1067.
[22]Koike K, Moriya K, Kimura S. Role of hepatitis C virus in the development of hepatocellular carcinoma:transgenic approach to viral hepatocarcinogenesis. J Gastroenterol Hepatol.2002; 17(4):394-400.
[23]Kamegaya Y, Hiasa Y, Zukerberg L, Fowler N, Blackard JT, Lin W, Choe WH, Schmidt EV, Chung RT. Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology.2005; 41(3):660-667.
[24]Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology.2002; 122(2): 352-365.
[25]Unoura M, Kobayashi K, Fukuoka K, Matsushita F, Morimoto H, Oshima T, Kaneko S, Hattori N, Murakami S, Yoshikawa H. Establishment of a cell line from a woodchuck hepatocellular carcinoma. Hepatology.1985; 5(6):1106-1111.
[26]Abe K, Kurata T, Yamada K, Okumura H, Shikata T. Establishment and characterization of a woodchuck hepatocellular carcinoma cell line (WH44KA). Jpn J Cancer Res.1988; 79(3):342-349.
[27]Lee H, Kawaguchi T, Nomura K, Kitagawa T. Establishment and characterization of a diethylnitrosamine-initiated woodchuck hepatocyte cell line. Hepatology.1987; 7(5): 937-940.
[28]Ohnishi S, Aoyama H, Shiga J, Itai Y, Moriyama T, Ishikawa T, Sasaki N, Yamamoto K, Koshimizu K, Kaneko S. Establishment of a new cell line from a woodchuck hepatocellular carcinoma. Hepatology.1988; 8(1):104-107.
[29]Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985; 230(4730):1157-1160.
[30]Babinet C, Farza H, Morello D, Hadchouel M, Pourcel C. Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. Science.1985; 230(4730):1160-1163.
[31]Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell.1989; 59(6):1145-1156.
[32]Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature.1991; 351(6324):317-320.
[33]Koike K. Hepatitis B virus HBx gene and hepatocarcinogenesis. Intervirology.1995; 38(3-4):134-142.
[34]Milich DR, Jones JE, Hughes JL, Maruyama T, Price J, Melhado I, Jirik F. Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice. J Immunol.1994; 152(2):455-466.
[35]Wang Y, Cui F, Lv Y, Li C, Xu X, Deng C, Wang D, Sun Y, Hu G, Lang Z, Huang C, Yang X. HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology.2004; 39(2):318-324.
[36]Park US, Su JJ, Ban KC, Qin L, Lee EH, Lee YI. Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin Bl. Gene.2000; 251(1):73-80.
[37]Dunsford HA, Sell S, Chisari FV. Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res.1990;50(11):3400-3407.
[38]Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS. Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. Mol Carcinog.1996; 15(4):261-269.
[39]Yu DY, Moon HB, Son JK, Jeong S, Yu SL, Yoon H, Han YM, Lee CS, Park JS, Lee CH, Hyun BH, Murakami S, Lee KK. Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein. J Hepatol.1999; 31(1):123-132.
[40]Lee TH, Finegold MJ, Shen RF, DeMayo J L, Woo SL, Butel JS. Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J Virol.1990; 64(12): 5939-5947.
[41]Zheng Y, Chen WL, Louie SG, Yen TS, Ou JH. Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice. Hepatology.2007; 45(1):16-21.
[42]Barone M, Leo DA, Maiorano E, Panella E, Scavo MP, Castellaneta A, Francavilla D, Francioso A. Role of sex steroid hormones on hepatocellular carcinoma (HCC) development in HBV transgenic mice. Dig Liver Dis.2007; 39(3):A23-24.
[43]Levrero M. Viral hepatitis and liver cancer:the case of hepatitis C. Oncogene.2006; 25(27):3834-3847.
[44]Ray RB, Lagging LM, Meyer K, Ray R. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol. 1996; 70(7):4438-4443.
[45]Ray RB, Meyer K, Ray R. Suppression of apoptotic cell death by hepatitis C virus core protein. Virology.1996; 226(2):176-182.
[46]McLauchlan J. Properties of the hepatitis C virus core protein:a structural protein that modulates cellular processes. J Viral Hepat.2000; 7(1):2-14.
[47]Tellinghuisen TL, Rice CM. Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol.2002; 5(4):419-427.
[48]Tanaka N, Moriya K, Kiyosawa K, Koike K, Aoyama T. Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice:implications for HCV-associated hepatocarcinogenesis. Int J Cancer.2008; 122(1):124-131.
[49]Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B. Infectious agents and cancer:criteria for a causal relation. Semin Cancer Biol.2004; 14(6):453-471.
[50]Jacob JR, Sterczer A, Toshkov IA. Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors. Hepatology.2004; 39(4):1008-1016.
[51]Knowles BB, Howe CC, Aden DP, Yeager AE, Korba BE, Cote PJ, Buendia MA, Gerin JL, Tennant BC. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science.1980; 209(4455):497-499.
[52]Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature.1979:282(5739): 615-616.
[53]Busch SJ, Barnhart RL, Martin GA, Flanagan MA, Jackson RL. Differential regulation of hepatic triglyceride lipase and 3-hydroxy-3-methylglutaryl-CoA reductase gene expression in a human hepatoma cell line, HepG2. J Biol Chem.1990; 265(36): 22474-22479.
[54]Zannis VI, Breslow JL, SanGiacomo TR, Aden DP, Knowles BB. Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. Biochemistry.1981; 20(25):7089-7096.
[55]Jiao W, Miyazaki K, Kitajima Y. Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer.2002; 86(1):98-101.
[56]Takahashi M, Sato T, Sagawa T, Lu Y, Sato Y, Iyama S, Yamada Y, Fukaura J, Takahashi S, Miyanishi K, Yamashita T, Sasaki K, Kogawa K, Hamada H, Kato J, Niitsu Y, et al. E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor. Mol Ther.2002; 5(5 Pt 1):627-634.
[57]Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst.1977; 59(1):221-226.
[58]Heffelfinger SC, Hawkins HH, Barrish J, Taylor L, Darlington GJ. SK HEP-1:a human cell line of endothelial origin. In Vitro Cell Dev Biol.1992; 28A(2):136-142.
[59]Yan J, Yu Y, Wang N, Chang Y, Ying H, Liu W, He J, Li S, Jiang W, Li Y, Liu H, Wang H, Xu Y. LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. Oncogene.2004; 23(10): 1939-1949.
[60]Wang XW, Yuan JH, Zhang RG, Guo LX, Xie Y, Xie H. Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice. World J Gastroenterol.2001; 7(3):345-351.
[61]Monjardino J, Crawford E. Polypeptide profile of HBSAg excreted by a human hepatoma cell line. Virology.1979; 96(2):652-655.
[62]MacNab GM, Alexander JJ, Lecatsas G, Bey EM, Urbanowicz JM. Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer.1976; 34(5):509-515.
[63]Skelly J, Copeland JA, Howard CR, Zuckerman AJ. Hepatitis B surface antigen produced by a human hepatoma cell line. Nature.1979; 282(5739):617-618.
[64]Ling CQ, Li B, Zhang C, Zhu DZ, Huang XQ, Gu W, Li SX. Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann Oncol. 2005; 16(1):109-115.
[65]Li B, Gu W, Zhang C, Han KQ, Ling CQ. Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie.2006; 29(8-9):367-371.
[66]Park JG, Lee JH, Kang MS, Park KJ, Jeon YM, Lee HJ, Kwon HS, Park HS, Yeo KS, Lee KU. Characterization of cell lines established from human hepatocellular carcinoma. Int J Cancer.1995; 62(3):276-282
[67]Lee JH, Ku JL, Park YJ, Lee KU, Kim WH, Park JG. Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. World J Gastroenterol.1999; 5(4):289-295.
[68]Lou CY, Feng YM, Qian AR, Li Y, Tang H, Shang P, Chen ZN. Establishment and characterization of human hepatocellular carcinoma cell line FHCC-98. World J Gastroenterol.2004; 10(10):1462-1465.
[69]Wen JM, Huang JF, Hu L, Wang WS, Zhang M, Sham JS, Xu JM, Zeng WF, Xie D, Liang LJ, Guan XY. Establishment and characterization of human metastatic hepatocellular carcinoma cell line. Cancer Genet Cytogenet.2002; 135(1):91-95.
[70]Armengol C, Tarafa G, Boix L, Sole M, Queralt R, Costa D, Bachs O, Bruix J, Capella G. Orthotopic implantation of human hepatocellular carcinoma in mice:analysis of tumor progression and establishment of the BCLC-9 cell line. Clin Cancer Res.2004; 10(6): 2150-2157.
[71]Sun FX, Tang ZY, Liu KD, Xue Q, Gao DM, Yu YQ, Zhou XD, Ma ZC. Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens. J Cancer Res Clin Oncol.1996; 122(7):397-402.
[72]Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer.1999; 81(5):814-821.
[73]Li Y, Tang Y, Ye L, Liu B, Liu K, Chen J, Xue Q. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol.2003; 129(1):43-51.
[74]Li Y, Tang Y, Ye L, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol.2001:7(5):630-636.
[75]Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, Liu YK, Tang ZY. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol.2004; 130(8):460-468.
[76]Darlington GJ, Bernhard HP, Miller RA, Ruddle FH. Expression of liver phenotypes in cultured mouse hepatoma cells. J Natl Cancer Inst.1980; 64(4):809-819.
[77]Tatsumi T, Takehara T, Kanto T, Miyagi T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N. Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. Cancer Res.2001; 61(20):7563-7567.
[78]Yamashita YI, Shimada M, Hasegawa H, Minagawa R, Rikimaru T, Hamatsu T, Tanaka S, Shirabe K, Miyazaki JI, Sugimachi K. Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res.2001; 61(3): 1005-1012.
[79]Morris HP, Meranze DR. Induction and some characteristics of "Minimal Deviation" and other transplantable rat hepatomas. Recent Results Cancer Res.1974; 44:103-114.
[80]Kulas DT, Goldstein BJ, Mooney RA. The transmembrane protein-tyrosine phosphatase LAR modulates signaling by multiple receptor tyrosine kinases. J Biol Chem.1996; 271(2):748-754.
[81]Schock D, Kuo SR, Steinburg MF, Bolognino M, Sparks JD, Sparks CE, Smith HC. An auxiliary factor containing a 240-kDa protein complex is involved in apolipoprotein B RNA editing. Proc Natl Acad Sci U S A.1996; 93(3):1097-1102.
[82]Ryall J, Rachubinski RA, Nguyen M, Rozen R, Broglie KE, Shore GC. Regulation and expression of carbamyl phosphate synthetase I mRNA in developing rat liver and Morris hepatoma 5123D. J Biol Chem.1984; 259(14):9172-9176.
[83]Calviello G, Palozza P, Piccioni E, Maggiano N, Frattucci A, Franceschelli P, Bartoli GM. Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats:effects on proliferation and apoptosis. Int J Cancer.1998; 75(5):699-705.
[84]Barnard GF, Erickson SK, Cooper AD. Regulation of lipoprotein receptors on rat hepatomas in vivo. Biochim Biophys Acta.1986; 879(3):301-312.
[85]Benedict WF, Gielen JE, Owens IS, Niwa A, Bebert DW. Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. IV. Stimulation of the enzyme activity in established cell lines derived from rat or mouse hepatoma and from normal rat liver. Biochem Pharmacol.1973; 22(21):2766-2769.
[86]Sassier P, Bergeron M. Specific inhibition of cell proliferation in the mouse intestine by an aqueous extract of rabbit small intestine. Cell Tissue Kinet.1977; 10(3):223-231.
[87]Bradlaw JA, Casterline JL Jr. Induction of enzyme activity in cell culture:a rapid screen for detection of planar polychlorinated organic compounds. J Assoc Off Anal Chem.1979; 62(4):904-916.
[88]Haggerty DF, Young PL, Popjak G, Carnes WH. Phenylalanine hydroxylase in cultured hepatoxytes. I. Hormonal control of enzyme levels. J Biol Chem.1973; 248(1):223-232.
[89]Carb6 N, Lopez-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, Quinn LS, Lopez-Soriano FJ, Argiles JM. Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br J Cancer.2000; 83(4):526-531.
[90]Lin SB, Wu LC, Huang SL, Hsu HL, Hsieh SH, Chi CW, Au LC. In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha. J Hepatol.2000; 33(4):601-608.
[91]Ogawa K, Nakanishi H, Takeshita F. Establishment of rat hepatocellular carcinoma cell lines with differing metastatic potential in nude mice. Int J Cancer.2001; 91(6):797-802.
[92]Novicki DL, Jirtle RL, Michalopoulos G. Establishment of two rat hepatoma cell strains produced by a carcinogen initiation, phenobarbital promotion protocol. In Vitro.1983; 19(3 Pt 1):191-202.
[93]Li HF, Ling MY, Xie Y, Xie H. Establishment of a lymph node metastatic model of mouse hepatocellular carcinoma Hca-F cells in C3H/Hej mice. Oncol Res.1998; 10(11-12):569-573.
[94]Cespedes MV, Casanova I, Parreno M, Mangues R. Mouse models in oncogenesis and cancer therapy. Clin Transl Oncol.2006; 8(5):318-329.
[95]Killion JJ, Radinsky R, Fidler IJ. Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metastasis Rev.1998-1999; 17(3):279-284.
[96]Kerbel RS. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans:better than commonly perceived-but they can be improved. Cancer Biol Ther.2003; 2(4 Suppl 1):S134-139.
[97]Hoffman RM. Orthotopic metastatic mouse models for anticancer drug discovery and evaluation:a bridge to the clinic. Invest New Drugs.1999;17(4):343-359.
[98]Hoffman RM. Orthotopic metastatic (MetaMouse) models for discovery and development of novel chemotherapy. Methods Mol Med.2005; 111:297-322.
[99]Li Y, Tang ZY, Tian B, Ye SL, Qin LX, Xue Q, Sun RX. Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis:study in nude mice model and clinical patients. J Cancer Res Clin Oncol.2006; 132(8):515-520.
[100]Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics.2004; 3(1):73-81.
[101]Albini A. Tumor microenvironment, a dangerous society leading to cancer metastasis. From mechanisms to therapy and prevention. Cancer Metastasis Rev.2008; 27(1):3-4.
[102]Ji XN, Ye SL, Li Y, Tian B, Chen J, Gao DM, Chen J, Bao WH, Liu YK, Tang ZY. Contributions of lung tissue extracts to invasion and migration of human hepatocellular carcinoma cells with various metastatic potentials. J Cancer Res Clin Oncol.2003; 129(10):556-564.
[103]Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer.2007; 7(9):645-658.
[104]Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature.2001; 414(6859):105-111.
[105]Alison MR, Lovell MJ. Liver cancer:the role of stem cells. Cell Prolif.2005; 38(6): 407-421.
[106]Sell S, Leffert HL. Liver cancer stem cells. J Clin Oncol.2008; 26(17):2800-2805.
[107]Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene.2008; 27(12):1749-1758.
[108]Talmadge JE, Singh RK, Fidler IJ, Raz A. Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol.2007; 170(3):793-804.
[109]Tamano S, Merlino GT, Ward JM. Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. Carcinogenesis.1994; 15(9):1791-1798.
[110]Liu G, McDonnell TJ, Montes de Oca Luna R, Kapoor M, Mims B, El-Naggar AK, Lozano G. High metastatic potential in mice inheriting a targeted p53 missense mutation. Proc Natl Acad Sci U S A.2000; 97(8):4174-4179.
[111]Neumann CA, Krause DS, Carman CV. Essential role for the peroxiredoxin Prdxl in erythrocyte antioxidant defence and tumour suppression. Nature.2003; 424(6948): 561-565.
[112]Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS. Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. Am J Pathol.1996; 149(2):407-428.
[113]Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest.2004; 113(12):1774-1783.
[114]Damo LA, Snyder PW, Franklin DS. Tumorigenesis in p27/p53-and pl8/p53-double null mice:functional collaboration between the pRb and p53 pathways. Mol Carcinog. 2005; 42(2):109-120.
[115]Cheo DL, Burns DK, Meira LB, Houle JF, Friedberg EC. Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/-mice. Cancer Res.1999; 59(4):771-775.
[116]D Dubois N, Bennoun M, Allemand I, Molina T, Grimber G, Daudet-Monsac M, Abelanet R, Briand P. Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J Hepatol.1991; 13(2):227-239.