摘要
背景与目的:结肠腺瘤性息肉病基因(adenomatous polyposis coli,APC)蛋白表达产物是Wnt信号转导途径重要组成部分,该基因失活使β-catenin蛋白降解障碍,从而使Tcf/Lef激活,引起基因异常转录,最终产生癌变。启动子区甲基化是导致抑癌基因转录失活的重要机制。本研究探讨乳腺癌APC基因启动子1A区甲基化状态与其蛋白表达的关系,并分析APC基因异常甲基化与乳腺癌临床病理特征的关系。方法:应用甲基化特异性PCR和免疫组织化学方法检测76例乳腺癌及相应癌旁乳腺组织中APC基因启动子1A区甲基化状态以及蛋白表达。结果:癌旁乳腺组织中均未发现APC基因启动子1A区甲基化,乳腺癌组织中APC基因启动子1A区甲基化率为36.8%。癌旁乳腺组织中APC蛋白阳性率为100%,乳腺癌中APC蛋白阳性率为52.4%。乳腺癌组织中APC基因甲基化与APC蛋白表达呈负相关(r=-0.351,P<0.05),与TNM分期呈正相关(r=0.335,P<0.05)。结论:乳腺癌发展过程中APC基因启动子1A区出现异常甲基化,是导致该蛋白表达缺失的主要原因,是导致该基因失活的重要机制之一。
BACKGROUND ＆ OBJECTIVE： Protein expression product of adenomatous polyposis coli （APC） gene is an important component of Wnt signal transduction pathway. APC gene inactivation leads to dysfunction of β-catenin protein degradation, and then activates Tcf/Lef and causes abnormal transcription of oncogenes, such as c-myc, c-jun and cyclin D1, finally leads to carcinogenesis, This study was to investigate the correlation of methylation status of APC gene promoter 1A to protein expression of APC gene in breast cancer, and analyze the correlation of aberrant methylation of APC gene to clinicopathologic features of breast cancer, METHODS.. Methylation status of APC gene promoter 1A in 76 specimens of breast cancer and corresponding adjacent tissues was detected by methylation-specific polymerase chain reaction; the expression of APC protein was detected by immunohisto- chemistry. RESULTS： The methylation rate of APC gene promoter 1A was significantly higher in breast cancer than in pericancerous normal breast tissue （36.8% vs.0,P〈0.05）.The positive rate of APC protein was significantly lower in breast cancer than in normal breast tissue （52.4% vs.100%, P〈0.05）.The promoter methylation of APC gene was positively correlated to TNM stage （r=0.296, P〈0.05）,but negatively correlated to the expression of APC protein （r=-0,368, P〈0.05）. CONCLUSION： Abnormal methylation of APC gene occurs in the progression of breast cancer, which is the main cause for the absence of APC protein expression, and the major mechanism of inactivation of APC gene.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2007年第6期586-590,共5页
Chinese Journal of Cancer
关键词
乳腺肿瘤
APC基因
甲基化
蛋白表达
Breast neoplasm
Adenomatous polyposis coil （APC） gene
Methylation
Protein expression
