摘要
目的 探讨不同化疗敏感性浆液性卵巢癌组织中BRCA1的表达水平及介导BRCA1表达的表观遗传学分子机制。方法选取化疗敏感与化疗耐药的卵巢癌组织标本各10例,利用实时荧光定量PCR方法验证差异化疗敏感性的卵巢癌组织中BRCA1的表达特点;采用焦磷酸测序技术分析这些差异化疗敏感性的卵巢癌标本中BRCA1基因启动子区域1~4位点的甲基化水平;采用回归分析研究BRCA1基因差异的甲基化位点与BRCA1表达的相关性。结果 化疗耐药的卵巢癌组织BRCA1表达水平显著升高,同时耐药组BRCA1基因核心启动子区域1~4位点甲基化水平降低;值得注意的是,位点4甲基化水平降低最明显,同时与BRCA1表达呈显著负相关。结论 研究结果提示,BRCA1基因启动子核心区域位点4的甲基化水平降低,可能显著影响BRCA1的转录调节及其相关的卵巢癌化疗敏感性。
Objective To investigate the expression of BRCAI in chemosensitive and chemoresistant ovarian cancer specimens, so as to provide a novel insight into the epigenetic mechanism involved in BRCAI transcription. Methods Serous ovarian cancer patients （ 10 chemesensitive and 10 chemoresistant cancer ） were enrolled for the study. B R CA 1 levels was analyzed by real-time quantitative PCR. The methylation levels of BR CA I core promoter （sites 1-4） was determined by pyrosequencing. Regression analysis was used to examine the possible relationship between BRCA I levels and the methylation levels of sites 1-4 in ovarian cancer specimens. Results Compared to chemesensitive ovarian cancer tissues, BRCA1 levels were increased, but the methylation levels of BR CA I core promoter （sites 1-4 ） were decreased in chemoresistant ovarian cancer tissues. How- ever, it is interesting to note that only a significant inverse correlation was observed between BRCAI levels and the methylated levels of site 4 （r =-0.612, P 〈 0.05 ）. Conclusion Our findings imply that the methylation levels of site 4 in the core promoter of BR CA 1 may be widely involved in the regulation of BRCA1 expression and chemosensitivity in ovarian cancer.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2016年第5期385-388,393,共5页
Journal of China Medical University
基金
国家自然科学基金(81402130)
辽宁省临床能力建设项目(LNCCC-A01-2015)
