摘要
目的研究WWOX蛋白在乳腺癌组织和细胞系中的表达变化，分析其与WWOX基因启动子和第一外显子CpG岛甲基化的关系。方法应用免疫组织化学染色检测乳腺癌组织和细胞系中WWOX蛋白表达，采用甲基化特异性PCR（methylation—specific PCR，MSP）分析乳腺癌组织和细胞系中WWOX基因CpG岛甲基化状况。结果32．2％的乳腺癌组织和5．4％正常乳腺组织中WWOX蛋白表达缺失，差异有统计学意义（P〈0．01）。乳腺癌组织WWOX表达异常与绝经后状态（P〈0．01）关系密切。Ⅰ、Ⅱ、Ⅲ期患者中WWOX蛋白表达缺失的比例分别为23．1％、28．6％和46．2％。55％的乳腺癌组织WWOX启动子CpG岛甲基化扩增，45％的乳腺癌组织WWOX第一外显子CpG岛甲基化扩增，癌旁组织中未出现CpG岛甲基化扩增。MDA—MB-231细胞WWOX基因CpG岛完全甲基化，而MCF-7细胞无甲基化产物扩增。结论乳腺癌中广泛存在着WWOX基因CpG岛甲基化，是WWOX表达缺陷的重要机制，并且可能通过性激素受体信号途径在乳腺癌的发生、发展中发挥作用。
Objective To evaluate the expression of WWOX gene in breast cancer and its relation to hypermethylation of WWOX gene CpG island. Methods The expression of WWOX protein was evaluated by immunohistochemical staining in breast cancer cell line and breast cancer tissues. Methylation specific PCR （MSP） was used to check whether it was methylated in the promoter and exon 1 of WWOX. Results Deletion in the WWOX expression was observed more frequently in invasive breast tumors （ 32. 2% ） than normal breast tissues （ 5.4% ） （ P 〈 0. 01 ）. 20. 3 % of premenopause cases were completely negative for WWOX expression compared to 57.2% of postmenopause breast carcinomas （ P 〈 0. 01 ）. Furthermore, 23.1% of Stage Ⅰ （6/26）, 28.6% of Stage Ⅱ （10/35）, 46.2% of Stage Ⅲ （12/26） tumors showed negative WVOX protein expression. In breast cancer specimens, methylation rate of promoter and exon 1 CpG island of WWOX gene was 55% and 45% respectively. Whereas, WWOX CpG islands of normal mammary tissues were completely unmethylated in all cases. CpG islands of WWOX promoter and exon 1 were methylated in MDA-MB-231 cell line but not MCF-7 cell. Conclusions Some deletion in WWOX expression is common in breast cancer and methylation of WWOX DNA CpG islands plays a crucial role in the silence of WWOX. WWOX may play a role in the carcinogenesis and development of breast cancer.
出处
《中华普通外科杂志》
CSCD
北大核心
2008年第5期380-383,共4页
Chinese Journal of General Surgery
基金
山东省自然科学基金项目（Y2006C30）
济南市“十一五”科技攻关项目（061033-2）
