摘要
背景:DNA或RNA分子异常甲基化导致的抑癌基因沉默、突变或其他功能性障碍是胃癌发生的关键机制之一。最近研究发现alkB基因产物具有修复DNA和mRNA碱基异常甲基化、纠正基因突变、复制转录障碍等功能,但对其在胃癌及其癌前病变组织中的表达情况尚不了解。目的:探讨alkB基因在胃癌及其癌前病变组织中的表达改变。方法:收集11例胃癌、癌旁和远离癌灶正常黏膜组织以及107例慢性萎缩性胃炎和121例非萎缩性胃炎患者的内镜活检黏膜,应用基因表达谱芯片实验评估alkB基因在各组织中的表达。以逆转录聚合酶链反应(RT-PCR)检验上述结果。结果:与远离癌灶正常黏膜组织相比,alkB基因在胃癌中的表达降低(Ratio值为0.208);与非萎缩性胃炎黏膜组织相比,alkB基因在萎缩性胃炎黏膜组织中的表达降低(Ratio值为0.378);而alkB基因在癌旁和远离癌灶正常黏膜组织中的表达无显著差异(Ratio值为0.726)。结论:alkB基因在胃癌和萎缩性胃炎黏膜组织中的表达下调,可能参与了胃癌发生过程中基因甲基化紊乱的机制。alkB基因是有潜在研究价值的分子靶标。
Background: Transcriptional silencing of tumor suppressor genes, mutation and other functional disturbance produced by DNA or RNA hypermethylation play a crucial role in the development of gastric cancer. Recent studies have demonstrated that alkB gene product can repair the hypermethylation of DNA and mRNA, restore the biological function of mRNA and tRNA inactivated by methylation and replicate the transcriptional impairment, but its expression in gastric cancer and precancerous lesions has not been clarified. Aims: To appraise the changes of alkB gene expression in tissues of human gastric cancer and its precancerous lesions. Methods: Eleven cases of gastric cancer, paracancerous and noncancerous mucosal tissues, mucosal tissues from endoscopic biopsies of 107 patients with atrophic gastritis and 121 patients with non-atrophic gastritis were collected, cDNA microarray was used as a tool for assessment genes expression in different tissues, and the results were reexamined by reverse transcriptase polymerase chain reaction (RT-PCR). Results: Compared with non-cancerous mucosal tissue, the expression of alkB gene were down-regulated in gastric cancer (Ratio value was 0.208); compared with non-atrophic gastritis mucosal tissue, the expression of alkB gene was lower in atrophic gastritis mucosal tissue (Ratio value was 0.378); but no significant difference was found between paracancerous and non-cancerous mucosal tissues (Ratio value was 0.726). Conclusions: The down-regulation of alkB gene expression in gastric cancer and atrophic gastritis mucosal tissue may be involved in the mechanism of hypermethylation of tumor suppressor genes owing to development of gastric cancer, and is of potential value in the future study of the molecular target.
出处
《胃肠病学》
2007年第7期401-404,共4页
Chinese Journal of Gastroenterology
基金
国家自然科学基金项目(30570827)
上海市重点学科建设项目(Y0205)资助
关键词
基因
ALKB
胃肿瘤
胃炎
萎缩性
寡核苷酸序列分析
DNA甲基化
Gene, alkB
Stomach Neoplasms
Gastritis, Atrophic
Oligonucleotide Array Sequence Analysis
DNA Methylation