中华普通外科杂志
中華普通外科雜誌
중화보통외과잡지
CHINESE JOURNAL OF GENERAL SURGERY
2008年
5期
380-383
,共4页
王晓%孙靖中%陈连胜%田斌%孙涛%金广超%马国辉%臧益秀
王曉%孫靖中%陳連勝%田斌%孫濤%金廣超%馬國輝%臧益秀
왕효%손정중%진련성%전빈%손도%금엄초%마국휘%장익수
乳腺肿瘤%基因表达%WWOX%CpG岛%甲基化
乳腺腫瘤%基因錶達%WWOX%CpG島%甲基化
유선종류%기인표체%WWOX%CpG도%갑기화
Breast neoplasms%Gene expression%WWOX%CpG island%Methylation
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.
目的 研究WWOX蛋白在乳腺癌組織和細胞繫中的錶達變化,分析其與WWOX基因啟動子和第一外顯子CpG島甲基化的關繫.方法 應用免疫組織化學染色檢測乳腺癌組織和細胞繫中WWOX蛋白錶達,採用甲基化特異性PCR(methylation-specific PCR,MSP)分析乳腺癌組織和細胞繫中WWOX基因CpG島甲基化狀況.結果 32.2%的乳腺癌組織和5.4%正常乳腺組織中WWOX蛋白錶達缺失,差異有統計學意義(P＜0.01).乳腺癌組織WWOX錶達異常與絕經後狀態(P＜0.01)關繫密切.Ⅰ、Ⅱ、Ⅲ期患者中WWOX蛋白錶達缺失的比例分彆為23.1%、28.6%和46.2%.55%的乳腺癌組織WWOX啟動子CpG島甲基化擴增,45%的乳腺癌組織WWOX第一外顯子CpG島甲基化擴增,癌徬組織中未齣現CpG島甲基化擴增.MDA-MB-231細胞WWOX基因CpG島完全甲基化,而MCF-7細胞無甲基化產物擴增.結論 乳腺癌中廣汎存在著WWOX基因CpG島甲基化,是WWOX錶達缺陷的重要機製,併且可能通過性激素受體信號途徑在乳腺癌的髮生、髮展中髮揮作用.
목적 연구WWOX단백재유선암조직화세포계중적표체변화,분석기여WWOX기인계동자화제일외현자CpG도갑기화적관계.방법 응용면역조직화학염색검측유선암조직화세포계중WWOX단백표체,채용갑기화특이성PCR(methylation-specific PCR,MSP)분석유선암조직화세포계중WWOX기인CpG도갑기화상황.결과 32.2%적유선암조직화5.4%정상유선조직중WWOX단백표체결실,차이유통계학의의(P＜0.01).유선암조직WWOX표체이상여절경후상태(P＜0.01)관계밀절.Ⅰ、Ⅱ、Ⅲ기환자중WWOX단백표체결실적비례분별위23.1%、28.6%화46.2%.55%적유선암조직WWOX계동자CpG도갑기화확증,45%적유선암조직WWOX제일외현자CpG도갑기화확증,암방조직중미출현CpG도갑기화확증.MDA-MB-231세포WWOX기인CpG도완전갑기화,이MCF-7세포무갑기화산물확증.결론 유선암중엄범존재착WWOX기인CpG도갑기화,시WWOX표체결함적중요궤제,병차가능통과성격소수체신호도경재유선암적발생、발전중발휘작용.
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 breasttissues(5.4%)(P＜0.01).20.3% of premenopause eases 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)tunlors showed negative WWOX 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.
