Id_1与Id_3在非小细胞肺癌中的表达及临床意义
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摘要
目的探索分化抑制因子(Inhibitors of differentiation,Id)Id_1和Id_3在非小细胞肺癌中的表达情况,分析其与肺癌的淋巴结转移,及与患者预后等的关系。
方法收集重庆医科大学第一附属医院胸心外科2004年至2007年非小细胞肺癌病人术后的石蜡标本60例,根据其年龄、性别,肿瘤的病理学类型,有无淋巴结转移情况等,分别进行分组对照。术后病理结果均经重庆医科大学病理科诊断证实。继而应用免疫组化SP法测定标本中Id_1和Id_3的表达情况,按SP试剂盒介绍的方法进行。Id_1、Id_3阳性信号为胞浆内出现黄色至棕褐色染色,采用染色强度×染色细胞百分率综合记分方式评估,将不同组别中Id_1和Id_3的表达情况进行对照分析,并将所有非小细胞肺癌样本中Id_1和Id_3的表达情况进行相关性分析.
结果在人非小细胞肺癌组织中,Id_1和Id_3均过度表达,与正常肺组织及良性病变组织(结核和炎性假瘤)比较差异具有显著性(P<0.01);在不同年龄、性别及病理类型中表达的差异无统计学意义(P>0.05);在肿瘤有淋巴结转移组中表达的明显高于无淋巴结转移组,统计分析差异具有显著性(P<0.05)。相关性分析示:Id_1和Id_3在非小细胞肺癌中表达呈正相关。
结论Id_1、Id_3蛋白与非小细胞肺癌的发生发展及淋巴结转移有关,而与患者的年龄、性别、肿瘤的病理类型等无关。Id_1和Id_3在非小细胞肺癌中正协同表达参与了肿瘤的发生。目前认为有无淋巴结转移是决定肺癌分期、治疗方法及判断预后的重要参照指标,因此,Id_1和Id_3蛋白可能作为非小细胞肺癌诊断、决定治疗方案及判断预后的重要标志物之一,这为非小细胞肺癌的诊断和治疗提供了新的研究思路。
Objective: To study the expression of Id_1 and Id_3 in human non-small cell lung cancer (NSCLC), and to analyze its potential clinical significance.
Methods: 60 paraffin-embedded specimens were collected and the specimens were got from the patients with NSCLC in the first affiliated hospital of Chongqing Medical University from 2004 to 2007. The cases were separately grouped according to the age, gender, pathological type of tumor, lymph node metastasis, etc. The pathological results were all confirmed by the department of pathology of Chongqing Medical University. Then, the expression of Id_1 and Id_3 were detected by immunohistochemical staining technique. The positive signals of Id_1 and Id_3 were the yellow or brown staining in intracytoplasm. We used the method of staining intensity×staining cells to analyze the results. We had done the contrast analysis to find out the reasons of the different expression of Id_1 and Id_3 in each group and the correlation analysis to find out the relationship of Id_1 and Id_3 in all NSCLC samples.
Results: There were no Id_l or Id_3 expressions in normal lung tissue, Negative to weak expression of those could be observed in benign disease tissues. However, the expressions of Id_1 and Id_3 were obviously strong in NSCLC, which was significantly higher than that in benign disease (P<0.01). Furthermore, the over expressions of Id_1 and Id_3 significantly correlated with lymph node metastasis (P<0.05) ,and they were not related to pathological type, the age or the gender of the patients(P>0.05). The correlation analysis showed positive correlation of them.
Conclusion: Id_l and Id_3 protein are overexpressed in NSCLC and the positive expression is correlated with lymph node metastasis. It suggested that Id_l and Id_3 are associated with tumorigenesis, invasion and metastasis in NSCLC. Id_l and Id_3 might be used as new markers of diagnosis and prognosis for NSCLC.This finding might put forward a new method for NSCLC treatment.
方法收集重庆医科大学第一附属医院胸心外科2004年至2007年非小细胞肺癌病人术后的石蜡标本60例,根据其年龄、性别,肿瘤的病理学类型,有无淋巴结转移情况等,分别进行分组对照。术后病理结果均经重庆医科大学病理科诊断证实。继而应用免疫组化SP法测定标本中Id_1和Id_3的表达情况,按SP试剂盒介绍的方法进行。Id_1、Id_3阳性信号为胞浆内出现黄色至棕褐色染色,采用染色强度×染色细胞百分率综合记分方式评估,将不同组别中Id_1和Id_3的表达情况进行对照分析,并将所有非小细胞肺癌样本中Id_1和Id_3的表达情况进行相关性分析.
结果在人非小细胞肺癌组织中,Id_1和Id_3均过度表达,与正常肺组织及良性病变组织(结核和炎性假瘤)比较差异具有显著性(P<0.01);在不同年龄、性别及病理类型中表达的差异无统计学意义(P>0.05);在肿瘤有淋巴结转移组中表达的明显高于无淋巴结转移组,统计分析差异具有显著性(P<0.05)。相关性分析示:Id_1和Id_3在非小细胞肺癌中表达呈正相关。
结论Id_1、Id_3蛋白与非小细胞肺癌的发生发展及淋巴结转移有关,而与患者的年龄、性别、肿瘤的病理类型等无关。Id_1和Id_3在非小细胞肺癌中正协同表达参与了肿瘤的发生。目前认为有无淋巴结转移是决定肺癌分期、治疗方法及判断预后的重要参照指标,因此,Id_1和Id_3蛋白可能作为非小细胞肺癌诊断、决定治疗方案及判断预后的重要标志物之一,这为非小细胞肺癌的诊断和治疗提供了新的研究思路。
Objective: To study the expression of Id_1 and Id_3 in human non-small cell lung cancer (NSCLC), and to analyze its potential clinical significance.
Methods: 60 paraffin-embedded specimens were collected and the specimens were got from the patients with NSCLC in the first affiliated hospital of Chongqing Medical University from 2004 to 2007. The cases were separately grouped according to the age, gender, pathological type of tumor, lymph node metastasis, etc. The pathological results were all confirmed by the department of pathology of Chongqing Medical University. Then, the expression of Id_1 and Id_3 were detected by immunohistochemical staining technique. The positive signals of Id_1 and Id_3 were the yellow or brown staining in intracytoplasm. We used the method of staining intensity×staining cells to analyze the results. We had done the contrast analysis to find out the reasons of the different expression of Id_1 and Id_3 in each group and the correlation analysis to find out the relationship of Id_1 and Id_3 in all NSCLC samples.
Results: There were no Id_l or Id_3 expressions in normal lung tissue, Negative to weak expression of those could be observed in benign disease tissues. However, the expressions of Id_1 and Id_3 were obviously strong in NSCLC, which was significantly higher than that in benign disease (P<0.01). Furthermore, the over expressions of Id_1 and Id_3 significantly correlated with lymph node metastasis (P<0.05) ,and they were not related to pathological type, the age or the gender of the patients(P>0.05). The correlation analysis showed positive correlation of them.
Conclusion: Id_l and Id_3 protein are overexpressed in NSCLC and the positive expression is correlated with lymph node metastasis. It suggested that Id_l and Id_3 are associated with tumorigenesis, invasion and metastasis in NSCLC. Id_l and Id_3 might be used as new markers of diagnosis and prognosis for NSCLC.This finding might put forward a new method for NSCLC treatment.
引文
[1] Lin CQ, Singh J, Murata K, eta1. A role for Id1 in the aggressive phenotype and steroid horm one response of human breast cancer cells[J]. Cancer Res, 2000, 60(5): 1332-1340.
[2] Ouyang XS, Wang X, Lee DT, et a1. Over expression of Id1 in prostate cancer[J]. J Urol, 2002, 167(6): 2598-2602.
[3] Kebebew E, Treseler PA, Dun QY, et a1. The helix-lop-helix prorein, Id1, is over expressed and regulates growth in papillary thyroid cancer[J]. Surgery, 2003, 134(2): 235-241.
[4] Lee TK, Man K, Ling MT. et a1. Over expression of Id1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16(INK4a)/RB pathway [J]. Carcinogenesis, 2003, 24(11): 1729-1736.
[5] Polsky D, Young AZ, Busam KJ, et a1. The transcriptional repressor of p16(INK4a), Idl, is up-regulated in early melanomas [J]. Cancer Res, 2001, 61(16): 6008-6011.
[6] Leesnansaksiri W, Wang H, Gooya JM, et a1. IL-3 induces inhibitor of DNA-binding protein-1 in hemopoietic progenitor cells and promotes myeloid cell development[J]. J Immunol, 2005,174(11): 7014-7021.
[7] Gerson Rothschild, Xudong Zhao, Antonio Iavarone, et a1. E proteins and Id2 converge on p57Kip2 to regulate cell cycle in neural Cells[J]. Molecular and Cellular biology, June 2006, p: 4351–4361
[8]刘欣,曾少举,何大澄,等.分化抑制因子Id在若干种癌及永生性细胞中的表达[J].中国生物工程杂志,2004,24(3):62-72
[9] Schindl M, Oberhuber G, Obermair A, et al.Over expression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer[J]. Cancer Res, 2001, 61(15): 5703-5706.
[10] Takai N, Miyazaki T, Fujisawa K, et a1. Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma[J]. Cancer Lett,2001, 165(2): 185-193
[11]汪萍,李晓军,贾丽,等.分化抑制因子Id2和Id3在肿瘤细胞中的表达[J].医学研究生学报, 2007, 20(1): 20-23
[12] Wang Q, Tao SW, Fu S, et a1. Over expression of Id1 in gastric adenocarcinoma implication for a novel diagnostic marker[J]. Anticancer Res, 2004, 24(2B): 881-886.
[13] Ling MT, Wang X, Ouyang XS, et a1.Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth[J]. Oncogene, 2002, 21(55): 8498-8505.
[14] Electron Kebebew, Miao Peng, Patrick A, et al. Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid Cancer Cells[J]. J Clin Endocrinol Metab, 2004 Dec, 89(12): 6105-11.
[15] Niekoloff BJ, Chaturvedi V, Bacon P, et al. Id1 delays senescence but does not immortalize keratinocytes[J]. J Biol Chem, 2000, 275(36): 27501-27504.
[16] Lee TK, Man K, Ling MT, et al. Over expression of Id1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16(INK4a)/RB pathway[J]. Carcinogenesis, 2003, 24(11): 1729-1736.
[17] Coppe JP, Itahan a Y, More DH, et al. Id-1 and Id-2 proteins as molecular markem for human prostate cancer progression[J]. Clin Cancer Res, 2004, 10(6): 2044-2051
[18] Schoppmann SF, Schindl M, Bayer G, et al. Over expression of Id-1 is associated witll poor clinical outcome in node negative breast cancer[J]. Lm J Cancer, 2003, 104(6): 677—682.
[19] Tsuchiya, Takeshi, Okaji, et al. Targeting Idl and Id3 inhibits peritoneal metastasis of gastric cancer[J]. Cancer Science, 2005, 96(11): 784—790.
[20] Arnold JM, Mok SC, Purdie D, et al. Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas[J]. Br J Cancer, 2001, 84(3): 352-359.
[21] Ming-Tat Lingy, Tracy C.M.Lauy, Chun Zhou, et al. Over expression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF).[J] Carcinogenesis, 2005, 26(10) : 1668–1676.
[22] VandepuRe D, Troost D, Leenstra S, et al. Expression and distribution of id helix-lop -helix proteins in human astrocytic tumors[J]. Gila, 2002, 38(4): 329—338.
[23] Anna Lasorella1, Takuma Uo1 and Antonio Iavarone. Id proteins at the cross-road of development and cancer[J]. Oncogene ,2001, 20: 8326 -8333.
[24] Tang J, Gordon GM, Nickolof BJ, et a1. The helix-loop-helix protein ld-l delays onset of replicative senescence in human endo-thelial cells[J]. Lab Invest, 2002, 82(8): 1073-1079
[25] Ling MT, Kwok WK, Fung MK, et a1. Proteasome mediated degradation of Id-1 is associated with TNFa1pha-induced apoptosis in prostate cancer cell.[J]. Carcinogenesis, 2006, 27(2): 205-215.
[1] Zoe Zebedee Z , Hara E . Id proteins in cell cycle control and cellular senescence[J]. Oncogene (2001) 20, 8317- 8325.
[2] Kim NS,Kim HJ,Koo BK,et a1.Receptor activator of NF- kap-paB ligand regulates the proliferation of mammary epithelial cellsvia Id2[j].Mol Cell Biol,2006,26(3) 1002—1013
[3] Hun H,Zhang YQ,Dabernat S,et a1.BMP4 regulates pancreat—ic progenitor cell expansion through Id2[J].J Biol Chem,2006,281(19) 13574—13580
[4] Leeanansaksiri W ,Wang H,Gooya JM ,et a1.II一3 induces in—hibitor of DNA-binding protein一1 in hemopoietic progenitor cellsand promotes myeloid cell development[J].J Immunol,2005,174(11):7014 7021
[5] Gerson Rothschild, Xudong Zhao, Antonio Iavarone, Anna Lasorella. E Proteins and Id2 Converge on p57Kip2 To Regulate Cell Cycle in Neural Cells[J] MOLECULAR AND CELLULAR BIOLOGY, June 2006, p. 4351–4361
[6] Chaudhary J,Sadler-Riggleman I,Ague JM,et a1.The helixloop-helix inhibitor of differentiation (ID)proteins induce post—mitotic terminally differentiated Sertoli ceils to re-enter the cellcycle and proliferate[J].Bid Reprod,2005,72(5):1205—1217
[7]刘欣,曾少举,何大澄,彭安,王永潮.分化抑制因子Id在若干种癌及永生性细胞中的表达[J]中国生物工程杂志,2004.24(3)62-72
[8] Lin CQ,Singh J,Murata K,et a1.A role for Id一1 in the aggressivephenotype and steroid horm one response of human breast cancer cells[J].Cancer Res,2000。60(5):1332—1340
[9] Takai N,Miyazaki T,Fujisawa K,et a1.Id1 expression is associat—ed with histological grade and invasive behavior in endometrial carcinoma[J].Cancer Lett,2001,165(2):185—193
[10] Schindl M,Oberhuber G,Obermair A,et a1.Overexpression ofId-·1 protein is a marker for unfavorable prognosis in early-stage cervical cancer[J].Cancer Res,2001,61(15):5703-5706.
[11]汪萍,李晓军,贾丽,马百坤,黄宇烽.分化抑制因子Id2和Id3在肿瘤细胞中的表达[J].医学研究生学报, 2007, 20(1): 20-23.
[12] Hiu-Fung Yuen, Chee-Wai Chua, Yuen-Piu Chan, et al. Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases[J] Modern Pathology (2006) 19, 931–941
[13] Electron Kebebew, Miao Peng, Patrick A, et al. Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid Cancer Cells[J]. J Clin Endocrinol Metab, 2004 Dec, 89(12): 6105-11.
[14] Maruyama H, Kleeff J, Wildi S, et al. Id-1 and Id-2 are overexpressed in pancreatic cancer and in dysplastic lesions in chronic pancreatitis. Am J Pathol 1999;155:815–822.
[15] Ming-Tat Lingy, Tracy C.M.Lauy, Chun Zhou,Chee Wai Chua, Wai Kei Kwok, Qi Wang,Xianghong Wang_ and Yong-Chuan Wong. Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF).[J] Carcinogenesis vol.26 no.10 pp.1668–1676, 2005
[16] Anna Lasorella1, Takuma Uo1 and Antonio Iavarone. Id proteins at the cross-road of development and cancer[J] Oncogene (2001) 20, 8326 -8333
[17]李晓军,汪萍等. Id3-EGFP融合基因表达载体的构建及其在人肺癌细胞A549中的表达[J]. Chin J Lab Meal, 006, 29(12): 1111-1115.
[18] Xue song Ouyang,Xiang hong Wang,Ming-Tat Ling,et al. Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16INK4a/pRB pathway[J].Carcinogenesis vol.23 no.5 pp.721-725,2002
[19] Ming-Tat Ling, Xianghong Wang1, Davy T.Lee1, P.C.Tam2, Sai-Wah Tsao1 and Yong-Chuan Wong. Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R)[J]. Carcinogenesis vol.25 no.4 pp.517?525, 2004
[20] Tang J.Gordon GM.Nickolof BJ,et a1.The helix-loop-helix pro-tein ld-l delays onset of replicative senescence in human endo-thelial cells[J].Lab Invest,2002,82(8):1073—1079
[21] Ling MT,Kwok WK,Fung MK,et a1.Proteasome mediated degradation of Id-1is associated with TNFa1pha-induced apoptosis in prostate cancer cell.[J] .Carcinogenesis,2006,27(2):205-215
[22] Damdinsuren B, Nagano H, Kondo M, et al. Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Int J Oncol 2005;26:319–327.
[23] Schindl M, Oberhuber G, Obermair A, et al. Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer. Cancer Res2001; 61:5703–5736.
[24] Umetani N, Takeuchi H, Fujimoto A, et al. Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis. Clin Cancer Res 2004; 10:7475–7483.
[25] Jang TJ, Jung KH, Choi EA. Id-1 gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer. Int J Cancer 2006; 118:1356–1363.
[26] Stighall M, Manetopoulos C, Axelson H, et al. High ID2 protein expression correlates with a favorable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells.Int J Cancer 2005;115:403–411.
[2] Ouyang XS, Wang X, Lee DT, et a1. Over expression of Id1 in prostate cancer[J]. J Urol, 2002, 167(6): 2598-2602.
[3] Kebebew E, Treseler PA, Dun QY, et a1. The helix-lop-helix prorein, Id1, is over expressed and regulates growth in papillary thyroid cancer[J]. Surgery, 2003, 134(2): 235-241.
[4] Lee TK, Man K, Ling MT. et a1. Over expression of Id1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16(INK4a)/RB pathway [J]. Carcinogenesis, 2003, 24(11): 1729-1736.
[5] Polsky D, Young AZ, Busam KJ, et a1. The transcriptional repressor of p16(INK4a), Idl, is up-regulated in early melanomas [J]. Cancer Res, 2001, 61(16): 6008-6011.
[6] Leesnansaksiri W, Wang H, Gooya JM, et a1. IL-3 induces inhibitor of DNA-binding protein-1 in hemopoietic progenitor cells and promotes myeloid cell development[J]. J Immunol, 2005,174(11): 7014-7021.
[7] Gerson Rothschild, Xudong Zhao, Antonio Iavarone, et a1. E proteins and Id2 converge on p57Kip2 to regulate cell cycle in neural Cells[J]. Molecular and Cellular biology, June 2006, p: 4351–4361
[8]刘欣,曾少举,何大澄,等.分化抑制因子Id在若干种癌及永生性细胞中的表达[J].中国生物工程杂志,2004,24(3):62-72
[9] Schindl M, Oberhuber G, Obermair A, et al.Over expression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer[J]. Cancer Res, 2001, 61(15): 5703-5706.
[10] Takai N, Miyazaki T, Fujisawa K, et a1. Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma[J]. Cancer Lett,2001, 165(2): 185-193
[11]汪萍,李晓军,贾丽,等.分化抑制因子Id2和Id3在肿瘤细胞中的表达[J].医学研究生学报, 2007, 20(1): 20-23
[12] Wang Q, Tao SW, Fu S, et a1. Over expression of Id1 in gastric adenocarcinoma implication for a novel diagnostic marker[J]. Anticancer Res, 2004, 24(2B): 881-886.
[13] Ling MT, Wang X, Ouyang XS, et a1.Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth[J]. Oncogene, 2002, 21(55): 8498-8505.
[14] Electron Kebebew, Miao Peng, Patrick A, et al. Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid Cancer Cells[J]. J Clin Endocrinol Metab, 2004 Dec, 89(12): 6105-11.
[15] Niekoloff BJ, Chaturvedi V, Bacon P, et al. Id1 delays senescence but does not immortalize keratinocytes[J]. J Biol Chem, 2000, 275(36): 27501-27504.
[16] Lee TK, Man K, Ling MT, et al. Over expression of Id1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16(INK4a)/RB pathway[J]. Carcinogenesis, 2003, 24(11): 1729-1736.
[17] Coppe JP, Itahan a Y, More DH, et al. Id-1 and Id-2 proteins as molecular markem for human prostate cancer progression[J]. Clin Cancer Res, 2004, 10(6): 2044-2051
[18] Schoppmann SF, Schindl M, Bayer G, et al. Over expression of Id-1 is associated witll poor clinical outcome in node negative breast cancer[J]. Lm J Cancer, 2003, 104(6): 677—682.
[19] Tsuchiya, Takeshi, Okaji, et al. Targeting Idl and Id3 inhibits peritoneal metastasis of gastric cancer[J]. Cancer Science, 2005, 96(11): 784—790.
[20] Arnold JM, Mok SC, Purdie D, et al. Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas[J]. Br J Cancer, 2001, 84(3): 352-359.
[21] Ming-Tat Lingy, Tracy C.M.Lauy, Chun Zhou, et al. Over expression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF).[J] Carcinogenesis, 2005, 26(10) : 1668–1676.
[22] VandepuRe D, Troost D, Leenstra S, et al. Expression and distribution of id helix-lop -helix proteins in human astrocytic tumors[J]. Gila, 2002, 38(4): 329—338.
[23] Anna Lasorella1, Takuma Uo1 and Antonio Iavarone. Id proteins at the cross-road of development and cancer[J]. Oncogene ,2001, 20: 8326 -8333.
[24] Tang J, Gordon GM, Nickolof BJ, et a1. The helix-loop-helix protein ld-l delays onset of replicative senescence in human endo-thelial cells[J]. Lab Invest, 2002, 82(8): 1073-1079
[25] Ling MT, Kwok WK, Fung MK, et a1. Proteasome mediated degradation of Id-1 is associated with TNFa1pha-induced apoptosis in prostate cancer cell.[J]. Carcinogenesis, 2006, 27(2): 205-215.
[1] Zoe Zebedee Z , Hara E . Id proteins in cell cycle control and cellular senescence[J]. Oncogene (2001) 20, 8317- 8325.
[2] Kim NS,Kim HJ,Koo BK,et a1.Receptor activator of NF- kap-paB ligand regulates the proliferation of mammary epithelial cellsvia Id2[j].Mol Cell Biol,2006,26(3) 1002—1013
[3] Hun H,Zhang YQ,Dabernat S,et a1.BMP4 regulates pancreat—ic progenitor cell expansion through Id2[J].J Biol Chem,2006,281(19) 13574—13580
[4] Leeanansaksiri W ,Wang H,Gooya JM ,et a1.II一3 induces in—hibitor of DNA-binding protein一1 in hemopoietic progenitor cellsand promotes myeloid cell development[J].J Immunol,2005,174(11):7014 7021
[5] Gerson Rothschild, Xudong Zhao, Antonio Iavarone, Anna Lasorella. E Proteins and Id2 Converge on p57Kip2 To Regulate Cell Cycle in Neural Cells[J] MOLECULAR AND CELLULAR BIOLOGY, June 2006, p. 4351–4361
[6] Chaudhary J,Sadler-Riggleman I,Ague JM,et a1.The helixloop-helix inhibitor of differentiation (ID)proteins induce post—mitotic terminally differentiated Sertoli ceils to re-enter the cellcycle and proliferate[J].Bid Reprod,2005,72(5):1205—1217
[7]刘欣,曾少举,何大澄,彭安,王永潮.分化抑制因子Id在若干种癌及永生性细胞中的表达[J]中国生物工程杂志,2004.24(3)62-72
[8] Lin CQ,Singh J,Murata K,et a1.A role for Id一1 in the aggressivephenotype and steroid horm one response of human breast cancer cells[J].Cancer Res,2000。60(5):1332—1340
[9] Takai N,Miyazaki T,Fujisawa K,et a1.Id1 expression is associat—ed with histological grade and invasive behavior in endometrial carcinoma[J].Cancer Lett,2001,165(2):185—193
[10] Schindl M,Oberhuber G,Obermair A,et a1.Overexpression ofId-·1 protein is a marker for unfavorable prognosis in early-stage cervical cancer[J].Cancer Res,2001,61(15):5703-5706.
[11]汪萍,李晓军,贾丽,马百坤,黄宇烽.分化抑制因子Id2和Id3在肿瘤细胞中的表达[J].医学研究生学报, 2007, 20(1): 20-23.
[12] Hiu-Fung Yuen, Chee-Wai Chua, Yuen-Piu Chan, et al. Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases[J] Modern Pathology (2006) 19, 931–941
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