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胃癌中E-cadherin和DAPK基因启动子异常甲基化的研究 被引量:3

Aberrant Methylation of Death-associated Protein Kinase and Epithelial Cadherin Promoters in Gastric Carcinoma
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摘要 目的:检测胃癌中死亡相关蛋白激酶(death-associated protein kinase,DAPK)基因和上皮钙粘蛋白(epithelialcadherill,E-cadherin)基因启动子区CpG岛甲基化状态,并探讨两个基因甲基化改变的特点及其与临床病理特征、患者一般资料之间的关系。方法:采用目前常用的甲基化特异性PCR(Methylation-specific PCR,MSP)方法检测41例胃癌组织和20例正常对照组织中DAPK、E-cadherin基因启动子区甲基化状态并进行统计分析。结果:41例胃癌组织中DAPK、E-cadherin基因启动子区甲基化阳性率分别为68.3%(28/41)和46.3%(19/41),20例正常对照组织中未检测到DAPK、E-cadherin基因启动子区发生甲基化,两个基因在胃癌组织中的甲基化率明显高于正常对照组织(P<0.05),但DAPK和E-cadherin基因启动子甲基化在胃癌的发生中无协同性(相关性和一致性)。胃癌组织中一个基因发生甲基化的检出率为78.0%(32/41);胃癌组织中DAPK基因启动子区甲基化与淋巴结转移、分化程度相关(P<0.05),而E-cadherin基因启动子区甲基化则与淋巴结转移和浸润深度有相关性(P<0.05),两个基因启动子区异常甲基化与被检查者肿瘤的大小、肿痛的部位等临床病理特征以及被检者的性别、年龄不具有相关性。结论:DAPK、E-cadherin基因启动子区甲基化是胃癌发生、发展过程中的频发事件,通过检测胃粘膜组织中两个基因启动子区甲基化状况,可能会对胃癌的早期诊断及判断预后提供一定的参考价值;联合检测两个基因甲基化状态优于各单个基因检测。 Objective: To detect the methylation status of the 5'CpG islands located in the promoter regions of the death-associated protein kinase (DAPK) and epithelial cadherin (E-cadherin) genes in gastric carcinoma, and to analyze the relationship between aberrant methylation of the two genes and clinicopathologic characteristics. Methods: We used methylation-specific polymerase chain reaction (MSP) to detect the methylation status of DAPK and E-cadherin genes in 41 gastric carcinoma tissues and 20 normal control tissues. The data were statistically analyzed. Results: The positive rate of methylation in the DAPK and E-cadherin promoter regions in the 41 gastric carcinoma tissues was 68.3% (28/41) and 46.3% (19/41), respectively, while no methylation was found in either promoter region in the 20 normal gastric mucosa tissues. Although the methylation rate of the two genes in gastric carcinoma tissues was higher than in normal control tissues (P〈 0.05), no correlation was found between DAPK promoter methylation and E-cadherin promoter methylation in gastric carcinoma. The combined rate of methylation in DAPK and E-cadherin promoter regions in the gastric carcinoma tissues was 78.05% (32/41). Methylation of the DAPK promoter in gastric carcinoma tissues was correlated with lymph node metastasis and differentiation level (P〈0.05). Methylation of the E-cadherin promoter in gastric carcinoma tissues was correlated with lymph node metastasis and depth of infiltration (P〈 0.05). Aberrantly methylated DAPK and E-cadherin promoter regions in gastric carcinoma were not correlated with tumor size, tumor location, patient age or gender. Conclusion: Aberrant methylation of DAPK and E-cadherin promoters is a common event in the development and progression of gastric carcinoma. Combined detection of methylation in these two genes may provide valuable information for the diagnosis and prognosis of gastric carcinoma.
出处 《中国肿瘤临床》 CAS CSCD 北大核心 2009年第7期383-387,共5页 Chinese Journal of Clinical Oncology
基金 国家自然科学基金资助(编号:30672383)~~
关键词 胃癌 DAPK基因 E—cadherin基因 启动子 甲基化 Gastric carcinoma DAPK gene E-cadherin gene Promoter Methylation
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  • 1Alvarez-Venegas R, Avramova Z. Methylation patterns of histone H3 Lys 4, Lys 9 and Lys 27 in transcriptionally active and inactive Arabidopsis genes and in atxl mutants.Nucleic Acids Res, 2005, 33(16):5199-5207.
  • 2Baylin S B. Tying it all together: epigenetics, genetics, cell cycle and cancer. Science, 1997, 277(5334):1948-1949.
  • 3Kanai Y, Ushijima S, Kondo Y, et al. DNA methyltransferase expression and DNA methylation of CpG island and pericentromeric satellite region in human colorectal and stomach cancers, Int J Cancer, 2001, 91(2): 205-212.
  • 4Tycko B. Epigenetic gene silencing in cancer. J Clin Invest,2000, 105(4): 401-407.
  • 5Nephew K P, Huang T H. Epigenetic gene silencing in cancer initiation and progression. Cancer Lett, 2003, 190(2):125-133.
  • 6Linggi B E, Brandt S J, Sun Z W, et al. Translating the histone code into leukemia. J Cell Biochem, 2005, 96(5): 938-950.
  • 7Yang X J, Ogryzko V V, Nishikawa J, et al. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature, 1996, 382(6589): 319-324.
  • 8Loprevite M, Tiseo M, Grossi F, et al. In vitro study of CI994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Oncol Res, 2005, 15(1): 39-48.
  • 9Mahadevan L C, Willis A C, Barratt M J. Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell,1991, 65(5): 775-783.
  • 10Nowak S J, Corces V G. Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation. Trends Genet, 2004, 20(4): 214-220.

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  • 1宋毅,袁淑兰,羊裔明,王修杰,黄光琦.丹参酮Ⅱ_A诱导白血病细胞凋亡过程中端粒酶活性的改变[J].中国中药杂志,2005,30(3):207-211. 被引量:16
  • 2王修杰,袁淑兰,黄韧敏,宋毅.Brdu和PCNA标记观察丹参酮对癌细胞增殖的影响[J].华西医科大学学报,1996,27(4):388-391. 被引量:27
  • 3胡礼炳,王国民,张利能,查锡良.膀胱癌细胞中DAPK基因启动子甲基化状态分析[J].中华实验外科杂志,2007,24(4):489-491. 被引量:13
  • 4Taby R,Issa JP.Cancer epigenetics[J].CA Cancer J Clin,2010,60(6):376-392.
  • 5Mack GS.Epigenetic cancer therapy makes headway[J].J Natl Cancer Inst,2006,98(20):1443-1444.
  • 6Lu Q,Zhang P,Zhang X,et al.Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer[J].Int J Mol Med,2009,24(6):773-780.
  • 7Lee WY,Liu KW,Yeung JH.Reactive oxygen species-mediated kinase activation by dihydrotanshinone in tanshinones-induced apoptosis in HepG2 cells[J].Cancer Lett,2009,285(1):46-57.
  • 8Cohen O,Inbal B,Kissil JL,et al.DAP-kinase participates in TNF-α and Fas-induced apoptosis and its function requires the death domain.J Cell Biol,1999,146:141-148.
  • 9Baylin SB,Herman JG,Graff JR,et al.Alterations in DNA methylation:a fundamental aspect of neoplasia.Adv Cancer Res,1998,72:141-196.
  • 10Raveh T,Droguett G,Horwitz MS,et al.DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transfo-rmation.Nat Cell Biol,2001,3:1-7.

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