S100A9和Hsp90β在大肠腺瘤和大肠癌中的表达及与临床病理相关性分析
|
摘要
目的：研究S100A9、Hsp90β在大肠腺瘤和大肠癌组织中的表达及其临床病理意义,初步探讨二者之间的关系。
方法：采用免疫组织化学染色SP方法和real time PCR方法检测53例正常大肠组织、31例大肠腺瘤组织、53例大肠癌组织中S100A9和Hsp90β的表达情况。所有数据用SPSS17.0分析。
结果：1、免疫组化实验：s100A9蛋白在大肠癌组织中的阳性表达率为61.3%(19／31),明显高于大肠腺瘤组织29.0%(9／31)和正常大肠组织22.6%(7／31),并且均存在显著性差异(P<0.05)；S100A9蛋白在大肠癌中的表达与组织分化程度有关,随着大肠腺癌分化程度的降低,S100A9的表达逐渐升高(P<0.05),与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。Hsp90β蛋白在大肠癌组织中的阳性表达率为45.2%(14／31),明显高于大肠腺瘤组织22.6%(7／31)和正常大肠组织19.4%(6／31),结果均存在显著性差异(P<0.05)；Hsp90β蛋白在大肠癌中的表达与组织分化程度有关,随着大肠腺癌分化程度的降低,Hsp90β的表达逐渐升高(P<0.05),与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。2、Real time PCR实验：S100A9mRNA、Hsp90βmRNA在大肠癌中的相对表达量明显高于大肠腺瘤、正常大肠组织,具有统计学意义(P<0.05)；在不同分化程度的大肠癌之间表达不同,随着大肠腺癌分化程度的降低,S100A9mRNA、Hsp90βmRNA的相对表达量逐渐升高(P<0.05)。3、在53例大肠癌组织中,S100A9与Hsp90β的表达呈正相关(P<0.05),而在大肠腺瘤和正常大肠组织中无明显相关性。
结论：1、S100A9、Hsp90β在大肠“正常组织-腺瘤-腺癌序列”中表达逐渐升高,提示S100A9和Hsp90β可以作为反映细胞分化程度的重要指标,与大肠腺癌的发生发展密切相关。2、随着大肠腺癌分化程度的降低,S100A9、Hsp90β的表达逐渐升高,与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。3、S100A9与Hsp90β在大肠癌中的表达呈密切正相关。结合病理形态学观察,同时检测S100A9与Hsp90β的表达,可以更客观判断大肠癌的分化程度。
Objective:To study the expression, clinicopathologic significance and relationship of S100A9 and Hsp90 beta in colorectal carcinoma and adenoma.
Methods:The expression of S100A9 and Hsp90 beta was determined in 53 cases of normal tissue samples,53 cases of colorectal carcinoma tissue samples,31 cases of colorectal adenoma tissue samples by SP immunohistochemical method and real time PCR. All data were analyzed by SPSS 17.0 statistic software.
Results:1. Immunohistochemistry:The positive rate of expression of S100A9 was 61.3% (19/31) in colorectal carcinoma,29.0%(9/31) in colorectal adenoma, and 22.6%(7/31) in normal tissue. Contrasted to colorectal adenoma and normal tissues, the expression of S100A9 in colorectal carcinoma obviously increased (P<0.05). The expression of S100A9 was positively correlated with histopathobigical grads (P＜0.05). As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of S100A9 gradually increased, but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage. The positive expression rate of Hsp90 beta was 45.2%(14/31) in colorectal carcinoma, 22.6%(7/31) in colorectal adenoma, and 19.4%(6/31) in normal tissue. Contrasted to colorectal adenoma and normal tissues, the expression of Hsp90 beta in colorectal carcinoma obviously increased (P<0.05). The expression of Hsp90βwas positively correlated with histopathobigical grads.As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of Hsp90 beta gradually increased (P<0.05), but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage.2. Real time PCR: The relative quantity of S100A9 mRNA and Hsp90 beta mRNA in colorectal carcinoma increased more than in colorectal adenoma and normal tissues (P<0.05), correlateing with histopathobigical grads (P<0.05).As the degree of differentiation of colorectal adenocarcinoma lowered, the relative quantity of S100A9 and Hsp90 beta gradually increased (P＜0.05).3. The expression of S100A9 was identically correlated with the expression of Hsp90 beta in colorectal carcinoma (P＜0.05), but not in normal tissue and colorectal adenoma.
Conclusion:1. The positive rates of expression of S100A9 and Hsp90 beta gradually increased in the sequence from normal tissue, adenoma to adenocarcinoma, which might be involved in carcinogenesis and progression in colorectal carcinoma, suggesting both S100A9 and Hsp90 beta may be important markers of reflecting the state of cell differentiation.2. As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of S100A9 and Hsp90 beta gradually increased (P<0.05), but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage.3. In colorectal carcinoma the expression of S100A9 is strong correlation with Hsp90 beta.Combination with pathological observation, the expression of S100A9 and Hsp90 beta may help us to distinguish the degree of differentiation and bionomics of colorectal adenocarcinoma.
方法：采用免疫组织化学染色SP方法和real time PCR方法检测53例正常大肠组织、31例大肠腺瘤组织、53例大肠癌组织中S100A9和Hsp90β的表达情况。所有数据用SPSS17.0分析。
结果：1、免疫组化实验：s100A9蛋白在大肠癌组织中的阳性表达率为61.3%(19／31),明显高于大肠腺瘤组织29.0%(9／31)和正常大肠组织22.6%(7／31),并且均存在显著性差异(P<0.05)；S100A9蛋白在大肠癌中的表达与组织分化程度有关,随着大肠腺癌分化程度的降低,S100A9的表达逐渐升高(P<0.05),与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。Hsp90β蛋白在大肠癌组织中的阳性表达率为45.2%(14／31),明显高于大肠腺瘤组织22.6%(7／31)和正常大肠组织19.4%(6／31),结果均存在显著性差异(P<0.05)；Hsp90β蛋白在大肠癌中的表达与组织分化程度有关,随着大肠腺癌分化程度的降低,Hsp90β的表达逐渐升高(P<0.05),与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。2、Real time PCR实验：S100A9mRNA、Hsp90βmRNA在大肠癌中的相对表达量明显高于大肠腺瘤、正常大肠组织,具有统计学意义(P<0.05)；在不同分化程度的大肠癌之间表达不同,随着大肠腺癌分化程度的降低,S100A9mRNA、Hsp90βmRNA的相对表达量逐渐升高(P<0.05)。3、在53例大肠癌组织中,S100A9与Hsp90β的表达呈正相关(P<0.05),而在大肠腺瘤和正常大肠组织中无明显相关性。
结论：1、S100A9、Hsp90β在大肠“正常组织-腺瘤-腺癌序列”中表达逐渐升高,提示S100A9和Hsp90β可以作为反映细胞分化程度的重要指标,与大肠腺癌的发生发展密切相关。2、随着大肠腺癌分化程度的降低,S100A9、Hsp90β的表达逐渐升高,与患者的年龄、性别、淋巴结转移、临床分期及肿瘤部位等因素无显著相关性。3、S100A9与Hsp90β在大肠癌中的表达呈密切正相关。结合病理形态学观察,同时检测S100A9与Hsp90β的表达,可以更客观判断大肠癌的分化程度。
Objective:To study the expression, clinicopathologic significance and relationship of S100A9 and Hsp90 beta in colorectal carcinoma and adenoma.
Methods:The expression of S100A9 and Hsp90 beta was determined in 53 cases of normal tissue samples,53 cases of colorectal carcinoma tissue samples,31 cases of colorectal adenoma tissue samples by SP immunohistochemical method and real time PCR. All data were analyzed by SPSS 17.0 statistic software.
Results:1. Immunohistochemistry:The positive rate of expression of S100A9 was 61.3% (19/31) in colorectal carcinoma,29.0%(9/31) in colorectal adenoma, and 22.6%(7/31) in normal tissue. Contrasted to colorectal adenoma and normal tissues, the expression of S100A9 in colorectal carcinoma obviously increased (P<0.05). The expression of S100A9 was positively correlated with histopathobigical grads (P＜0.05). As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of S100A9 gradually increased, but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage. The positive expression rate of Hsp90 beta was 45.2%(14/31) in colorectal carcinoma, 22.6%(7/31) in colorectal adenoma, and 19.4%(6/31) in normal tissue. Contrasted to colorectal adenoma and normal tissues, the expression of Hsp90 beta in colorectal carcinoma obviously increased (P<0.05). The expression of Hsp90βwas positively correlated with histopathobigical grads.As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of Hsp90 beta gradually increased (P<0.05), but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage.2. Real time PCR: The relative quantity of S100A9 mRNA and Hsp90 beta mRNA in colorectal carcinoma increased more than in colorectal adenoma and normal tissues (P<0.05), correlateing with histopathobigical grads (P<0.05).As the degree of differentiation of colorectal adenocarcinoma lowered, the relative quantity of S100A9 and Hsp90 beta gradually increased (P＜0.05).3. The expression of S100A9 was identically correlated with the expression of Hsp90 beta in colorectal carcinoma (P＜0.05), but not in normal tissue and colorectal adenoma.
Conclusion:1. The positive rates of expression of S100A9 and Hsp90 beta gradually increased in the sequence from normal tissue, adenoma to adenocarcinoma, which might be involved in carcinogenesis and progression in colorectal carcinoma, suggesting both S100A9 and Hsp90 beta may be important markers of reflecting the state of cell differentiation.2. As the degree of differentiation of colorectal adenocarcinoma lowered, the expression of S100A9 and Hsp90 beta gradually increased (P<0.05), but unrelated to age, sexuality, location of tumors, lymphonode metastasis, and Duke's stage.3. In colorectal carcinoma the expression of S100A9 is strong correlation with Hsp90 beta.Combination with pathological observation, the expression of S100A9 and Hsp90 beta may help us to distinguish the degree of differentiation and bionomics of colorectal adenocarcinoma.
引文
[1]Morson BC.Prevention of colorectal cancer J R Soc Med.1979 Feb; 72(2):83-5
[2]Volm M, Koomagi R, Mattern J, et al. Prognostic value of vascular endothelial growth facto r and its receptor Flt-1 in squamous cell lung cancer.Cancer,1997,74(4):64-70
[3]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma of the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour differ entiation. Eur J Cancer,2004,40(8):1179-87
[4]陈怡,冉志华,黄美兰,等.人结肠癌中热休克蛋白70、90 α和90β mRNA的表达及其意义.胃肠病学,2006,11(9)：526-529.
[5]Rasmussen R, Quantification on the Light Cycler Methods and Applications. Heidelberg,Springe r Press;2001.21
[6]Ravasi T, Hsu K, Goyette J, et al. Probing the S100 protein family through genomic and fun ctional analysis.Genomics,2004,84(1):10-22
[7]Yui S, Nakatani Y, Mikami M, et al. Calprotectin (S100A8/S100A9),an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity 7. Biol Pharm Bull,2003, 26(6):753-60
[8]Thorey IS, Roth J, Regenbogen J, et al. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem,2001,276(38):35818-25
[9]Itou H. Yao M, Fujita I, et al. The crystal structure of Human MRP14 (S100A9),a Ca (+)-d ependentRegulator Protein in inflammatory process.J Mol Biol,2002;316(2):265-276.
[10]Gebhardt C, Breitenbach U, Tuckermann JP, et al. Calgranulins S100A8 and S100A9 are ne gatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed througho ut skin carcinogenesis. Oncogene,2002,21(27):4266-76
[11]Berthier S, Paclet MH, Lerouge S, et al. Changing the conformation state of cytochrome b5 58 initiates NADPH oxidase activation:MRP8/MRP14 regulation. J Biol Chem,2003,278(28): 25499-508
[12]Ghavami S, Kerkhoff C, Los M, et al. Mechanism of apoptosis induced by S100A8/A9 in c olon cancer cell lines:the role of ROS and the effect of metal ions. J Leukoc Biol,2004,7 6(1):169-75
[13]Yui S, Nakatani Y, Mikami M, et al. Calprotectin(S100A8/S100A9),an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity. Biol pharm bull,2003, 26(6):753-60
[14]Ludwig S, Lein M, Stephan C, et al. S100A8, S100A9, and the S100A8/A9 Complex in Cir
culating Blood Are Not Associated With Prostate Cancer Risk A Re-Evaluation Study. The Pr ostate,2007,67(12):1301-07
[15]Rafii S, Lyden D.S100 chemokines mediate bookmarking of premetastatic niches. Nat Cell Bi ol,2006,8:1321-3
[16]Hiratsuka S, Watanabe A, Aburatani H, et al. Tumour-mediated up-regulation of chemoattract ants and recruitment of myeloid cells predetermines lung metastasis.Nat Cell Biol,2006,8(12): 1369-75
[17]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma o f the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour dif ferentiation. Eur J Cancer,2004,40(8):1179-87
[18]Alexander Hermani, Jochen Hess, et al. Calcium-Binding Proteins S100A8 and S100A9 as N ovel Diagnostic Markers in Human Prostate Cancer.Clinical Cancer Research,2005,11:5146-5 2
[19]Kim HJ, Kang HJ, Lee H, et al. Identification of S100A8 and S100A9 as serological marker s for colorectal cancer.J Proteome Res,2009,8(3):1368-79
[20]Wang J, Cai Y, Xu H, et al. Expression of MRP 14 gene is frequently down-regulated in Ch inese human esophageal cancer.Cell Res,2004,14(1):46-53.
[21]Roesch EM, Nees M, Karsai S, et al.Transcript and proteome analysis reveals reduced expres sion of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol,2005,84(2-3):431-41.
[22]Panaretou B, Siligardi G, Meyer P, et al. Activation of the ATPase activity of Hsp90 by the stress-regulated cochaperone Ahal. Mol Cell,2002,10(6):1307-18
[23]Fujita N, Sato S, Ishida A, et al. Involvement of HSP90 in signaling and stability of 3-phos phoinositide-dependent kinase-1. J Biol Chem,2002,277(12):10346-53
[24]Solit DB, Scher HI, Rosen N, et al. HSP90 as therapeutic target in prostate cancer. Semin O ncol,2003,30(5):709-716
[25]Simeone AM, Li YJ,Broemeling LD, et al. Cyclooxygenase-2 is essential for HER2/neu to su ppress N-(4-hydroxyphenyl)retinamide apoptotic effect in breast cancer cells. Cancer Res,2004, 64(4):1224-1228
[26]Hahn M, Li W, Yu C, et al. Rapamycin and UCN-01 synergistically induce apoptosis in hu man leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JN K signal transduction pathways. Mol Cancer Ther,2005,4(3):457-470
[27]施新岗,湛先保,李兆申,等.热休克蛋白与胃部疾病.胃肠病学,2004,9(2)：71-72
[28]朱勤,张阳德,胡煜,等.休克蛋白90 β在结肠癌组织中的表达及其意义.现代生物医学发展,2007,7(7)：1042-1044
[29]胡鹤本,朱人敏,吴波,等.热休克蛋白90 α在胃癌中的表达及其意义.中华消化内镜,2005,22(1)：52-53
[30]李海军,戴洁,张林西,等.HSP90 α蛋白在人结肠癌中的表达.世界华人消化杂志,2005,13(4)：56-568
[3l]刘宪玲,叶苓,王建波,等.热休克蛋白HSP90β在人胃癌组织及耐药细胞系中的表达.第四军医大学学报,2000,21(2)：131-134
[32]赵菊梅,刘涛,田聆,等.鼻咽癌HSP90 β的表达及临床意义.陕西医学杂志,2005,34(11)：1307-1309
[33]Georgakis GV, Li Y, Rassidakis GZ, et al. Inhibition of heat shock protein 90 function by 1 7-allylamio-17-demethoxygeldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinas e, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest and cell death. Clin Cancer Res,2006,12(2):584-590
[34]Broemer M, Krappmann D, Scheiolereit C, et al. Requirement of HSP90 activity for I kappa B Kinase(IKK) biosynthesis and for constitutive and inducible IKK and NF-KappaB activation. Oncogene,2004,23(31):5378-5386
[35]Sweeney CJ, Methrotra S, Sadaria MR, et al.The sesquiterpene lactone parthenolide in combi nation with docetaxel reduces metastasis and improves survival in a xenoguaft model of breas t cancer. Mol Cancer Ther,2005,4(6):1004-1012
[36]Hiratsuka S, Watanabe A, Sakurai Y, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol,2008,10(11):1349-55
[37]余畅,邓华瑜.HSP90与survivin在人乳腺癌细胞中的作用及机制探讨.肿瘤,2007,27(10)：791-794
[38]BowmanT,Garcia R,Turkson J, et al. STATs in oncogenesis.Oncogene,2000,19(21):2474-2488.
[39]Li C, Zhang F, Lin M,et al. Induction of S100A9 gene expression by cytokine oncostatin M in breast cancer cells through the STAT3 signaling cascade. Breast Cancer Res Treat,2004, 87(2):123-34
[1]Korndorfer IP, Brueckner F, Skerra A, et al. The crystal structure of the human (S100A8/S1 00A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-he lices can determine specific association of two EF-hand proteins. J Mol Biol,2007,370(5):887-9 8
[2]Hobbs JA, May R, Tanousis K, et al. Myeloid Cell Function in MRP-14 (S100A9) null mic e. Mol Cell Biol,2003,23(7):2564-76
[3]Ravasi T, Hsu K, Goyette J, et al. Probing the S100 protein family through genomic and fu nctional analysis. Genomics,2004,84(1):10-22
[4]Thorey IS, Roth J, Regenbogen J, et al. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem,2001,276(38):35818-25
[5]Itou H, Yao M, Fujita I, et al. The crystal structure of Human MRP14 (S100A9),a Ca (+)-d ependentRegulator Protein in inflammatory process.J Mol Biol,2002;316(2):265-276.
[6]Kane D, Roth J, Frosch M, et al. Increased perivascular synovial membrane expression of m yeloid-related proteins in psoriatic arthritis. Arthritis Rheum,2003,48:1676-1685.
[7]Wassell J, Dolmani S, Metzner M, et al. Faecal calprotectin:a new marker for Crohn's dise ase? Ann Clin Biochem,2004,41:230-223.
[8]Frosch M, Vogl T, Waldherr R, et al. Expression of MRP8 and MRP 14 by macrophages is a marker for severe forms of glomerulonephritis.J Leukoc Biol,2004,75; 198-206.
[9]Burkhardt K, Radespiel-Troger M, Rupprecht HD, et al. An increase in myeloid-related prote in serum levels precedes acute renal allograft rejection. J Am Soc Nephrol,2001,12:1947-1957.
[10]Hiratsuka S, Watanabe A, Sakurai Y, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol,2008,10(11):1349-55
[11]Gebhardt C, Breitenbach U, Tuckermann JP, et al. Calgranulins S100A8 and S100A9 are ne gatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed throughout skin carcinogenesis. Oncogene,2002,21(27):4266-76
[12]Berthier S, Paclet MH, Lerouge S, et al. Changing the conformation state of cytochrome b 558 initiates NADPH oxidase activation:MRP8/MRP14 regulation. J Biol Chem,2003,278(28):2 5499-508
[13]Moon A, Yong HY, Song JI, et al. Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion. Mol Cancer Re s,2008,6(10):1544-53
[14]Li C, Zhang F, Lin M, et al. Induction of S100A9 gene expression by cytokine oncostatin M in breast cancer cells through the STAT3 signaling cascade. Breast Cancer Res Treat,2004, 87(2):123-34
[15]Salama I, Malone PS, Mihaimeed F, et al. A review of the S100 proteins in cancer.Eur J Surg Oncol,2008,34(4):357-64
[16]Rafii S, Lyden D. S100 chemokines mediate bookmarking of premetastatic niches.Nat Cell Biol,2006,8:1321-3
[17]Hiratsuka S, Watanabe A, Aburatani H,et al. Tumour-mediated up-regulation of chemoattract ants and recruitment of myeloid cells predetermines lung metastasis.Nat Cell Biol,2006,8(12):13 69-75
[18]Ghavami S, Kerkhoff C, Los M, et al. Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines:the role of ROS and the effect of metal ions. J Leukoc Biol,2004,7 6(1):169-75
[19]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma of the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour diffe rentiation. Eur J Cancer,2004,40(8):1179-87
[20]Ito Y, Arai K, Ryushi, et al. S100A9 expression is significantly linked to Dedifferentiation of thyroid carcinoma. Pathol Res Pract,2005,201(8-9):551-6
[21]Arai K, Teratani T, Nozawa R, et al. Investigation of S100A9 expression in pulmonary ad enocarcinoma:S100A9 expression is associated with tumor differentiation.Oncol Rep,2001,8(3):5 91-6
[22]Sheikh AA, Vimalachandran D, Thompson CC, et al. The expression of S100A8 in pancrea tic cancer associated monocytes is associated with the Smad4 status of pancreatic cancer cells. P roteomics,2007,7(11):1929-40
[23]Li MX, Xiao ZQ, Liu YF, et al. Quantitative Proteomic Analysis of Differential Proteins in the Stroma of Nasopharyngeal Carcinoma and Normal Nasopharyngeal Epithelial Tissue.J Cellul ar Biochem,2009,106(4):570-9
[24]Yui S, Nakatani Y, Mikami M, et al. Calprotectin(S100A8/S100A9),an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity. Biol pharm bull,2003,2 6(6):753-60
[25]Hermani A, Hess J, De Servi B, et al. Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer.Clinical Cancer Research,2005,11(14):5146-52
[26]Kim HJ, Kang HJ, Lee H, et al. Identification of S100A8 and S100A9 as serological mark ers for colorectal cancer. J Proteome Res,2009,8(3):1368-79
[27]Ludwig S, Lein M, Stephan C, et al. S100A8, S100A9, and the S100A8/A9 Complex in C irculating Blood Are Not Associated With Prostate Cancer Risk A Re-Evaluation Study. The Pro state,2007,67(12):1301-07
[28]Wang J, Cai Y, Xu H, et al. Expression of MRP 14 gene is frequently down-regulated in Chinese human esophageal cancer. Cell Res,2004,14(1):46-53
[29]Roesch EM, Nees M, Karsai S, et al. Transcript and proteome analysis reveals reduced ex pression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol,2005,84(2-3):431-44
[30]冯旺琴,崔竹梅,刘芝华,等.S100A8和S100A9在子宫颈鳞癌组织中的表达.现代肿瘤医学,2008,16(11)：1969-72
[1]钟文英,普雄明.热休克蛋白的分子生物学研究进展.医学综述,2005,11(2)：148-150
[2]Nathan DF, Vos MH, Lindquist S.In vivo functions of the Saccharomyces cereviesiae HSP90 chaperone. Proc Natl Acad Sci USA,1997,94(24):12949-56
[3]Panaretou B, Siligardi G, Meyer P, et al. Activation of the ATPase activity of Hsp90 by the stress-regulated cochaperone Ahal. Mol Cell,2002,10(6):1307-18
[4]Otaka M, Odashima M, Watanabe S, et al. Role of heat shock proteins in intestinal mucosal protection. Biochem Biophys Res Commun,2006,348(1):1-5
[5]Schmidt S, Strub A, Voos W, et al. Protein translocation into mitochondria. BIol Signals Re cept,2001,10(4):14-25
[6]荣芳,侯恒.热休克蛋白与胃黏膜保护的研究.医学综述,2008,14(7)：9-11
[7]Fujita N, Sato S, Ishida A, et al. Involvement of HSP90 in signaling and stability of 3-phos phoinositide-dependent kinase-1.J Biol Chem,2002,277(12):10346-53
[8]赵月,徐洪涛,,戴顺东,等.热休克蛋白90抑制NH3T3成纤维细胞凋亡.中华组织化学与细胞化学杂志,2006,15(3)：266-270
[9]Solit DB, Scher HI, Rosen N, et al. HSP90 as therapeutic target in prostate cancer.Semin O ncol,2003,30(5):709-716
[10]Simeone AM, Li YJ, Broemeling LD, et al. Cyclooxygenase-2 is essential for HER2/neu to suppress N-(4-hydroxyphenyl)retinamide apoptotic effect in breast cancer cells. Cancer Res, 2004,64(4):1224-1228
[11]Hahn M, Li W, Yu C, et al. Rapamycin and UCN-01 synergistically induce apoptosis in h uman leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JNK signal transduction pathways. Mol Cancer Ther,2005,4(3):457-470
[12]Broemer M, Krappmann D, Scheiolereit C,et al. Requirement of HSP90 activity for I kappa B Kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF-KappaB activat ion. Oncogene,2004,23(31):5378-5386
[13]Sweeney CJ, Methrotra S, Sadaria MR, et al. The sesquiterpene lactone parthenolide in co mbination with docetaxel reduces metastasis and improves survival in a xenoguaft model of breast cancer. Mol Cancer Ther,2005,4(6):1004-1012
[14]施新岗,湛先保,李兆申,等.热休克蛋白与胃部疾病.胃肠病学,2004,9(2)：71-72
[15]朱勤,张阳德,胡煜,等.休克蛋白90 β在结肠癌组织中的表达及其意义.现代生物医学发展,2007,7(7)：1042-1044
[16]胡鹤本,朱人敏,等.热休克蛋白90 α在胃癌中的表达及其意义.中华消化内镜,2005,22(1)：52-53
[17]李海军,戴洁,张林西,等.HSP90α蛋白在人结肠癌中的表达.世界华人消化杂志,2005,13(4)：56-568
[18]刘宪玲,叶苓,王建波,等.热休克蛋白HSP90 β在人胃癌组织及耐药细胞系中的表达.第四军医大学学报,2000,21(2)：131-134
[19]赵菊梅,刘涛,田聆,等.鼻咽癌HSP90 β的表达及临床意义.陕西医学杂志,2005,34(11)：1307-1309
[20]Len N.Hsp 90 inhibitors as novel cancer chemotherapeutic agents.Trends Mol Med,2002,8(4): S55-S61.
[21]张剑军,徐惠绵,等.热休克蛋白70和90 α在人胃癌组织中表达及其与胃癌生物学行为的关系.中华肿瘤防治杂志,2006,13(7)：495-496
[22]Srivastava P.Roles of heat-shock proteins in innate and adaptive immunity.Nature Rev Immu nol,2002,2(3):185-194
[23]Srivastava PK. Immunotherapy for human cancer using heat shock protein-peptide complexe s.Curr Oncol Rep,2005,7(2):104-108
[24]Bucci M, Roviezzo F, Cicala C, et al. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucoc orticoid receptor in vivo. Br J Pharmacol,2000,131(1):13-16
[25]Georgakis GV, Li Y, Rassidakis GZ, et al. Inhibition of heat shock protein 90 function by 17-allylamio-17-demethoxygeldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest a nd cell death. Clin Cancer Res,2006,12(2):584-590
[26]Allan RK, Mok D, Ward Bk, et al. Modulation of chaperone function and cochaperone inte raction by novobiocin in the Cerminal domain of Hsp90:evidence that coumarin antibiotics disrupt Hsp90 dimerization. J Biol Chem,2006,281(11):7161-71.
[27]Wright L, Barril X, Dymock B, et al. Structure-activity relationships in purine-based inhibit or binding to Hsp90 isoforms. Chem Biol,2004, 11(6):775-785
[2]Volm M, Koomagi R, Mattern J, et al. Prognostic value of vascular endothelial growth facto r and its receptor Flt-1 in squamous cell lung cancer.Cancer,1997,74(4):64-70
[3]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma of the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour differ entiation. Eur J Cancer,2004,40(8):1179-87
[4]陈怡,冉志华,黄美兰,等.人结肠癌中热休克蛋白70、90 α和90β mRNA的表达及其意义.胃肠病学,2006,11(9)：526-529.
[5]Rasmussen R, Quantification on the Light Cycler Methods and Applications. Heidelberg,Springe r Press;2001.21
[6]Ravasi T, Hsu K, Goyette J, et al. Probing the S100 protein family through genomic and fun ctional analysis.Genomics,2004,84(1):10-22
[7]Yui S, Nakatani Y, Mikami M, et al. Calprotectin (S100A8/S100A9),an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity 7. Biol Pharm Bull,2003, 26(6):753-60
[8]Thorey IS, Roth J, Regenbogen J, et al. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem,2001,276(38):35818-25
[9]Itou H. Yao M, Fujita I, et al. The crystal structure of Human MRP14 (S100A9),a Ca (+)-d ependentRegulator Protein in inflammatory process.J Mol Biol,2002;316(2):265-276.
[10]Gebhardt C, Breitenbach U, Tuckermann JP, et al. Calgranulins S100A8 and S100A9 are ne gatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed througho ut skin carcinogenesis. Oncogene,2002,21(27):4266-76
[11]Berthier S, Paclet MH, Lerouge S, et al. Changing the conformation state of cytochrome b5 58 initiates NADPH oxidase activation:MRP8/MRP14 regulation. J Biol Chem,2003,278(28): 25499-508
[12]Ghavami S, Kerkhoff C, Los M, et al. Mechanism of apoptosis induced by S100A8/A9 in c olon cancer cell lines:the role of ROS and the effect of metal ions. J Leukoc Biol,2004,7 6(1):169-75
[13]Yui S, Nakatani Y, Mikami M, et al. Calprotectin(S100A8/S100A9),an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity. Biol pharm bull,2003, 26(6):753-60
[14]Ludwig S, Lein M, Stephan C, et al. S100A8, S100A9, and the S100A8/A9 Complex in Cir
culating Blood Are Not Associated With Prostate Cancer Risk A Re-Evaluation Study. The Pr ostate,2007,67(12):1301-07
[15]Rafii S, Lyden D.S100 chemokines mediate bookmarking of premetastatic niches. Nat Cell Bi ol,2006,8:1321-3
[16]Hiratsuka S, Watanabe A, Aburatani H, et al. Tumour-mediated up-regulation of chemoattract ants and recruitment of myeloid cells predetermines lung metastasis.Nat Cell Biol,2006,8(12): 1369-75
[17]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma o f the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour dif ferentiation. Eur J Cancer,2004,40(8):1179-87
[18]Alexander Hermani, Jochen Hess, et al. Calcium-Binding Proteins S100A8 and S100A9 as N ovel Diagnostic Markers in Human Prostate Cancer.Clinical Cancer Research,2005,11:5146-5 2
[19]Kim HJ, Kang HJ, Lee H, et al. Identification of S100A8 and S100A9 as serological marker s for colorectal cancer.J Proteome Res,2009,8(3):1368-79
[20]Wang J, Cai Y, Xu H, et al. Expression of MRP 14 gene is frequently down-regulated in Ch inese human esophageal cancer.Cell Res,2004,14(1):46-53.
[21]Roesch EM, Nees M, Karsai S, et al.Transcript and proteome analysis reveals reduced expres sion of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol,2005,84(2-3):431-41.
[22]Panaretou B, Siligardi G, Meyer P, et al. Activation of the ATPase activity of Hsp90 by the stress-regulated cochaperone Ahal. Mol Cell,2002,10(6):1307-18
[23]Fujita N, Sato S, Ishida A, et al. Involvement of HSP90 in signaling and stability of 3-phos phoinositide-dependent kinase-1. J Biol Chem,2002,277(12):10346-53
[24]Solit DB, Scher HI, Rosen N, et al. HSP90 as therapeutic target in prostate cancer. Semin O ncol,2003,30(5):709-716
[25]Simeone AM, Li YJ,Broemeling LD, et al. Cyclooxygenase-2 is essential for HER2/neu to su ppress N-(4-hydroxyphenyl)retinamide apoptotic effect in breast cancer cells. Cancer Res,2004, 64(4):1224-1228
[26]Hahn M, Li W, Yu C, et al. Rapamycin and UCN-01 synergistically induce apoptosis in hu man leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JN K signal transduction pathways. Mol Cancer Ther,2005,4(3):457-470
[27]施新岗,湛先保,李兆申,等.热休克蛋白与胃部疾病.胃肠病学,2004,9(2)：71-72
[28]朱勤,张阳德,胡煜,等.休克蛋白90 β在结肠癌组织中的表达及其意义.现代生物医学发展,2007,7(7)：1042-1044
[29]胡鹤本,朱人敏,吴波,等.热休克蛋白90 α在胃癌中的表达及其意义.中华消化内镜,2005,22(1)：52-53
[30]李海军,戴洁,张林西,等.HSP90 α蛋白在人结肠癌中的表达.世界华人消化杂志,2005,13(4)：56-568
[3l]刘宪玲,叶苓,王建波,等.热休克蛋白HSP90β在人胃癌组织及耐药细胞系中的表达.第四军医大学学报,2000,21(2)：131-134
[32]赵菊梅,刘涛,田聆,等.鼻咽癌HSP90 β的表达及临床意义.陕西医学杂志,2005,34(11)：1307-1309
[33]Georgakis GV, Li Y, Rassidakis GZ, et al. Inhibition of heat shock protein 90 function by 1 7-allylamio-17-demethoxygeldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinas e, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest and cell death. Clin Cancer Res,2006,12(2):584-590
[34]Broemer M, Krappmann D, Scheiolereit C, et al. Requirement of HSP90 activity for I kappa B Kinase(IKK) biosynthesis and for constitutive and inducible IKK and NF-KappaB activation. Oncogene,2004,23(31):5378-5386
[35]Sweeney CJ, Methrotra S, Sadaria MR, et al.The sesquiterpene lactone parthenolide in combi nation with docetaxel reduces metastasis and improves survival in a xenoguaft model of breas t cancer. Mol Cancer Ther,2005,4(6):1004-1012
[36]Hiratsuka S, Watanabe A, Sakurai Y, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol,2008,10(11):1349-55
[37]余畅,邓华瑜.HSP90与survivin在人乳腺癌细胞中的作用及机制探讨.肿瘤,2007,27(10)：791-794
[38]BowmanT,Garcia R,Turkson J, et al. STATs in oncogenesis.Oncogene,2000,19(21):2474-2488.
[39]Li C, Zhang F, Lin M,et al. Induction of S100A9 gene expression by cytokine oncostatin M in breast cancer cells through the STAT3 signaling cascade. Breast Cancer Res Treat,2004, 87(2):123-34
[1]Korndorfer IP, Brueckner F, Skerra A, et al. The crystal structure of the human (S100A8/S1 00A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-he lices can determine specific association of two EF-hand proteins. J Mol Biol,2007,370(5):887-9 8
[2]Hobbs JA, May R, Tanousis K, et al. Myeloid Cell Function in MRP-14 (S100A9) null mic e. Mol Cell Biol,2003,23(7):2564-76
[3]Ravasi T, Hsu K, Goyette J, et al. Probing the S100 protein family through genomic and fu nctional analysis. Genomics,2004,84(1):10-22
[4]Thorey IS, Roth J, Regenbogen J, et al. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem,2001,276(38):35818-25
[5]Itou H, Yao M, Fujita I, et al. The crystal structure of Human MRP14 (S100A9),a Ca (+)-d ependentRegulator Protein in inflammatory process.J Mol Biol,2002;316(2):265-276.
[6]Kane D, Roth J, Frosch M, et al. Increased perivascular synovial membrane expression of m yeloid-related proteins in psoriatic arthritis. Arthritis Rheum,2003,48:1676-1685.
[7]Wassell J, Dolmani S, Metzner M, et al. Faecal calprotectin:a new marker for Crohn's dise ase? Ann Clin Biochem,2004,41:230-223.
[8]Frosch M, Vogl T, Waldherr R, et al. Expression of MRP8 and MRP 14 by macrophages is a marker for severe forms of glomerulonephritis.J Leukoc Biol,2004,75; 198-206.
[9]Burkhardt K, Radespiel-Troger M, Rupprecht HD, et al. An increase in myeloid-related prote in serum levels precedes acute renal allograft rejection. J Am Soc Nephrol,2001,12:1947-1957.
[10]Hiratsuka S, Watanabe A, Sakurai Y, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol,2008,10(11):1349-55
[11]Gebhardt C, Breitenbach U, Tuckermann JP, et al. Calgranulins S100A8 and S100A9 are ne gatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed throughout skin carcinogenesis. Oncogene,2002,21(27):4266-76
[12]Berthier S, Paclet MH, Lerouge S, et al. Changing the conformation state of cytochrome b 558 initiates NADPH oxidase activation:MRP8/MRP14 regulation. J Biol Chem,2003,278(28):2 5499-508
[13]Moon A, Yong HY, Song JI, et al. Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion. Mol Cancer Re s,2008,6(10):1544-53
[14]Li C, Zhang F, Lin M, et al. Induction of S100A9 gene expression by cytokine oncostatin M in breast cancer cells through the STAT3 signaling cascade. Breast Cancer Res Treat,2004, 87(2):123-34
[15]Salama I, Malone PS, Mihaimeed F, et al. A review of the S100 proteins in cancer.Eur J Surg Oncol,2008,34(4):357-64
[16]Rafii S, Lyden D. S100 chemokines mediate bookmarking of premetastatic niches.Nat Cell Biol,2006,8:1321-3
[17]Hiratsuka S, Watanabe A, Aburatani H,et al. Tumour-mediated up-regulation of chemoattract ants and recruitment of myeloid cells predetermines lung metastasis.Nat Cell Biol,2006,8(12):13 69-75
[18]Ghavami S, Kerkhoff C, Los M, et al. Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines:the role of ROS and the effect of metal ions. J Leukoc Biol,2004,7 6(1):169-75
[19]Arai K, Teratani T, Kuruto-Niwa R, et al. S100A9 expression in invasive ductal carcinoma of the breast:S100A9 expression in adenocarcinoma is closely associated with poor tumour diffe rentiation. Eur J Cancer,2004,40(8):1179-87
[20]Ito Y, Arai K, Ryushi, et al. S100A9 expression is significantly linked to Dedifferentiation of thyroid carcinoma. Pathol Res Pract,2005,201(8-9):551-6
[21]Arai K, Teratani T, Nozawa R, et al. Investigation of S100A9 expression in pulmonary ad enocarcinoma:S100A9 expression is associated with tumor differentiation.Oncol Rep,2001,8(3):5 91-6
[22]Sheikh AA, Vimalachandran D, Thompson CC, et al. The expression of S100A8 in pancrea tic cancer associated monocytes is associated with the Smad4 status of pancreatic cancer cells. P roteomics,2007,7(11):1929-40
[23]Li MX, Xiao ZQ, Liu YF, et al. Quantitative Proteomic Analysis of Differential Proteins in the Stroma of Nasopharyngeal Carcinoma and Normal Nasopharyngeal Epithelial Tissue.J Cellul ar Biochem,2009,106(4):570-9
[24]Yui S, Nakatani Y, Mikami M, et al. Calprotectin(S100A8/S100A9),an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity. Biol pharm bull,2003,2 6(6):753-60
[25]Hermani A, Hess J, De Servi B, et al. Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer.Clinical Cancer Research,2005,11(14):5146-52
[26]Kim HJ, Kang HJ, Lee H, et al. Identification of S100A8 and S100A9 as serological mark ers for colorectal cancer. J Proteome Res,2009,8(3):1368-79
[27]Ludwig S, Lein M, Stephan C, et al. S100A8, S100A9, and the S100A8/A9 Complex in C irculating Blood Are Not Associated With Prostate Cancer Risk A Re-Evaluation Study. The Pro state,2007,67(12):1301-07
[28]Wang J, Cai Y, Xu H, et al. Expression of MRP 14 gene is frequently down-regulated in Chinese human esophageal cancer. Cell Res,2004,14(1):46-53
[29]Roesch EM, Nees M, Karsai S, et al. Transcript and proteome analysis reveals reduced ex pression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol,2005,84(2-3):431-44
[30]冯旺琴,崔竹梅,刘芝华,等.S100A8和S100A9在子宫颈鳞癌组织中的表达.现代肿瘤医学,2008,16(11)：1969-72
[1]钟文英,普雄明.热休克蛋白的分子生物学研究进展.医学综述,2005,11(2)：148-150
[2]Nathan DF, Vos MH, Lindquist S.In vivo functions of the Saccharomyces cereviesiae HSP90 chaperone. Proc Natl Acad Sci USA,1997,94(24):12949-56
[3]Panaretou B, Siligardi G, Meyer P, et al. Activation of the ATPase activity of Hsp90 by the stress-regulated cochaperone Ahal. Mol Cell,2002,10(6):1307-18
[4]Otaka M, Odashima M, Watanabe S, et al. Role of heat shock proteins in intestinal mucosal protection. Biochem Biophys Res Commun,2006,348(1):1-5
[5]Schmidt S, Strub A, Voos W, et al. Protein translocation into mitochondria. BIol Signals Re cept,2001,10(4):14-25
[6]荣芳,侯恒.热休克蛋白与胃黏膜保护的研究.医学综述,2008,14(7)：9-11
[7]Fujita N, Sato S, Ishida A, et al. Involvement of HSP90 in signaling and stability of 3-phos phoinositide-dependent kinase-1.J Biol Chem,2002,277(12):10346-53
[8]赵月,徐洪涛,,戴顺东,等.热休克蛋白90抑制NH3T3成纤维细胞凋亡.中华组织化学与细胞化学杂志,2006,15(3)：266-270
[9]Solit DB, Scher HI, Rosen N, et al. HSP90 as therapeutic target in prostate cancer.Semin O ncol,2003,30(5):709-716
[10]Simeone AM, Li YJ, Broemeling LD, et al. Cyclooxygenase-2 is essential for HER2/neu to suppress N-(4-hydroxyphenyl)retinamide apoptotic effect in breast cancer cells. Cancer Res, 2004,64(4):1224-1228
[11]Hahn M, Li W, Yu C, et al. Rapamycin and UCN-01 synergistically induce apoptosis in h uman leukemia cells through a process that is regulated by the Raf-1/MEK/ERK, Akt, and JNK signal transduction pathways. Mol Cancer Ther,2005,4(3):457-470
[12]Broemer M, Krappmann D, Scheiolereit C,et al. Requirement of HSP90 activity for I kappa B Kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF-KappaB activat ion. Oncogene,2004,23(31):5378-5386
[13]Sweeney CJ, Methrotra S, Sadaria MR, et al. The sesquiterpene lactone parthenolide in co mbination with docetaxel reduces metastasis and improves survival in a xenoguaft model of breast cancer. Mol Cancer Ther,2005,4(6):1004-1012
[14]施新岗,湛先保,李兆申,等.热休克蛋白与胃部疾病.胃肠病学,2004,9(2)：71-72
[15]朱勤,张阳德,胡煜,等.休克蛋白90 β在结肠癌组织中的表达及其意义.现代生物医学发展,2007,7(7)：1042-1044
[16]胡鹤本,朱人敏,等.热休克蛋白90 α在胃癌中的表达及其意义.中华消化内镜,2005,22(1)：52-53
[17]李海军,戴洁,张林西,等.HSP90α蛋白在人结肠癌中的表达.世界华人消化杂志,2005,13(4)：56-568
[18]刘宪玲,叶苓,王建波,等.热休克蛋白HSP90 β在人胃癌组织及耐药细胞系中的表达.第四军医大学学报,2000,21(2)：131-134
[19]赵菊梅,刘涛,田聆,等.鼻咽癌HSP90 β的表达及临床意义.陕西医学杂志,2005,34(11)：1307-1309
[20]Len N.Hsp 90 inhibitors as novel cancer chemotherapeutic agents.Trends Mol Med,2002,8(4): S55-S61.
[21]张剑军,徐惠绵,等.热休克蛋白70和90 α在人胃癌组织中表达及其与胃癌生物学行为的关系.中华肿瘤防治杂志,2006,13(7)：495-496
[22]Srivastava P.Roles of heat-shock proteins in innate and adaptive immunity.Nature Rev Immu nol,2002,2(3):185-194
[23]Srivastava PK. Immunotherapy for human cancer using heat shock protein-peptide complexe s.Curr Oncol Rep,2005,7(2):104-108
[24]Bucci M, Roviezzo F, Cicala C, et al. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucoc orticoid receptor in vivo. Br J Pharmacol,2000,131(1):13-16
[25]Georgakis GV, Li Y, Rassidakis GZ, et al. Inhibition of heat shock protein 90 function by 17-allylamio-17-demethoxygeldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest a nd cell death. Clin Cancer Res,2006,12(2):584-590
[26]Allan RK, Mok D, Ward Bk, et al. Modulation of chaperone function and cochaperone inte raction by novobiocin in the Cerminal domain of Hsp90:evidence that coumarin antibiotics disrupt Hsp90 dimerization. J Biol Chem,2006,281(11):7161-71.
[27]Wright L, Barril X, Dymock B, et al. Structure-activity relationships in purine-based inhibit or binding to Hsp90 isoforms. Chem Biol,2004, 11(6):775-785