胃癌p21WAF1基因表达及组蛋白乙酰化关系初步探究.docVIP

胃癌p21WAF1基因表达及组蛋白乙酰化关系初步探究 　 作者：童洪飞，林胜璋，倪仲琳，游涛，张伟，郑志强 【摘要】 目的:探讨胃癌组织p21WAF1基因表达与组蛋白乙酰化的关系。方法:利用RT-PCR对53例原发性胃癌的癌组织、癌旁组织和正常胃黏膜的p21WAF1 mRNA表达进行分析；同时对其中p21WAF1 mRNA表达失活或表达量不足癌旁和正常黏膜的1/2的7例患者进行乙酰化组蛋白免疫印迹分析。结果:①胃癌组织中的p21WAF1表达率和表达值均显著低于正常胃黏膜和癌旁组织。②p21WAF1表达水平在分化较好和分化较差的胃癌组织间差异没有显著性 (P＞0.05)，但在不同浸润深度及有/无淋巴结转移的胃癌组织中差异具有显著性 (P＜0.05，P＜0.01)。③ p21WAF1 mRNA表达失活或表达量不足癌旁和正常黏膜的1/2的7例患者中有5例（5/7，71.43%）总染色质乙酰化组蛋白H3表达水平明显低于其相应的癌旁和正常黏膜，甚至在检测水平以下。结论:胃癌组织p21WAF1的表达降低至少部分归因于组蛋白乙酰化水平的低下。 【关键词】 胃癌；p21WAF1；组蛋白乙酰化 Abstract: Objective:To investigate the relationship between p21WAF1 gene expression and histone acetylation in gastric cancer. Methods: p21WAF1 gene expression of cancer tissue, para-focus of cancer and normal tissue in 53 cases with primary gastric cancer were analyzed with RT-PCR, meanwhile, histone acetylation in 7 cases with p21WAF1 mRNA non-expression or expression less than half of para-focus of cancer and normal tissue were analyzed with Western blot hybridization. Results:① Both p21WAF1 expression ratio and value of gastric cancer were lower than those of para-focus of cancer and normal tissue. ② p21WAF1 expression level had no difference between well-differentiated and poorly-differentiated gastric cancer (Pgt;0.05), but there was significantly difference in different invasion depth and had none lymph node metastasis (Plt;0.05, Plt;0.01). ③ The expression of acetylated histone-H3 in total chromatin of 5 cases (5/7, 71.43%) was significantly lower than those of para-focus of cancer and normal tissue corresponding to them, even under detective level. Conclusion: The lower expression of p21WAF1 in gastric cancer is partly due to lower level of histone acetylation. Key words: gastric cancer；p21WAF1；histone acetylation 胃癌的发生同其他肿瘤一样，有癌基因的过度表达和（或）抑癌基因的失活。而在基因表达的调控中，表观遗传修饰已经成为共识，主要内容包括染色质的组蛋白乙酰化。组蛋白通过其乙酰化/去乙酰化来调控基因的表达与沉默。目前关于组蛋白乙酰化修饰对p21WAF1基因表达的调控在胰腺癌、结肠癌、乳腺癌等方面研究较多[1-3]，而在胃癌方面的研究报道甚少。本研究通过观察组蛋白乙酰化对p21WAF1基因转录和表达的影响，初步探讨p21WAF1基因在胃癌发生发展中的作用，以及染色质组蛋白乙酰化水平与p21WAF1基因表达的关系。 1