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| PTCH1基因甲基化在胃癌发病中的作用 |
| 左云,高军,李兆申*,宋宇,涂建成,程志健,王浩,丰宇芳,陈亚楠,刘苏霞,龚燕芳 |
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| (第二军医大学长海医院消化内科,上海 200433) |
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| 摘要: |
| 目的:探讨PTCH1基因甲基化在胃癌发生中的作用及去甲基化试剂5-氮杂-2′-脱氧胞苷(5-Aza-dC)对胃癌的治疗作用。方法:选取10例胃癌组织及其癌旁正常组织和胃癌细胞株AGS,抽提组织和细胞的总RNA和基因组DNA。实时定量QRT-PCR检测PTCH1基因的mRNA表达,MSP(methylation specific PCR)分析PTCH1基因启动子区甲基化变化。用5-Aza-dC处理AGS细胞株,流式细胞术检测细胞周期和凋亡并观察PTCH1基因甲基化水平的改变。结果:胃癌组织、癌旁正常组织和胃癌细胞株AGS中PTCH1基因表达和启动子甲基化水平呈负相关,相关系数为-0.591（P=0.006）;5-Aza-dC的处理可引起胃癌细胞AGS细胞发生凋亡和G0/G1期阻滞,PTCH1基因发生去甲基化变化并表达增加。结论: PTCH1基因启动子区高甲基化是胃癌细胞PTCH1低表达主要原因之一,5-Aza-dC能逆转PTCH1基因甲基化状态,调控其表达,对胃癌具有一定的治疗作用。 |
| 关键词: 胃肿瘤 PTCH1基因 Hedgehog信号通路 DNA甲基化 5-氮杂-2′-脱氧胞苷 |
| DOI：10.3724/SP.J.1008.2009.0884 |
| 投稿时间：2009-01-01修订日期：2009-04-20 |
| 基金项目: |
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| Role of PTCH1 gene hypermethylation in tumorigenesis of gastric cancer |
| ZUO Yun,GAO Jun,LI Zhao-shen*,SONG Yu,TU Jian-cheng,CHENG Zhi-jian,WANG Hao,FENG Yu-fang,CHEN Ya-nan,LIU Su-xia,GONG Yan-fang |
| (Department of Gastroenterology,Changhai Hospital,Second Military Medical University,Shanghai 200433,China) |
| Abstract: |
| Objective:To study the effect of PTCH1 methylation on gastric carcinogenesis and the therapeutic effect of methylation inhibitor,5-aza-2′-deoxyeytidine (5-aza-dC), for treatment of gastric cancer.Methods: The total RNAs were extracted from 10 gastric cancer tissues,their corresponding adjacent normal tissues, and gastric cancer cell line AGS.The PTCH1 mRNA expression was detected by Quantitative real-time PCR (QRT-PCR) and the methylation of the promoter was examined by methylation specific PCR (MSP).AGS cells were treated by 5-Aza-dC; the cell cycle and apoptosis were examined by flow cytometry,and the methylation level was also observed.Results: PTCH1 expression was negatively correlated with promoter methylation in gastric cancer tissues,their corresponding adjacent normal tissues, and gastric cancer cell line AGS(r=-0.591,P=0.006).5-Aza-dC treatment caused apoptosis and G0/G1 phase arrest of AGS cells,and also induced demethylation of PTCH1 and increased its expression.Conclusion: Hypermethylation of PTCH1 gene promoter region is one of the main causes of low PTCH1 expression in AGS cells.Demethylation agent 5-Aza-dC can reverse this methylation status of PTCH1 and regulate the expression of PTCH1,suggesting a role for it in gastric cancer treatment. |
| Key words: stomach neoplasms PTCH1 gene hedgehog signal pathway methylation 5-aza-2′-deoxyeytidine |
