摘要
应用核酸分子杂交、ＰＣＲ、ＰＣＲ－ＡＳＯ杂交等技术，对人宫颈癌中Ｈａ－ｒａｓ等三种癌基因、ＨＰＶ１６病毒基因及Ｐ５３、Ｒｂ抑癌基因等多基因变化及其致癌机理进行了研究。结果表明：①宫颈癌中存在Ｈａ－ｒａｓ第１２位密码子Ｇ→Ｔ点突变，突变率为１８．２％（８／４４），并有Ｈａ－ｒａｓ基因扩增，扩增率为４５％（９／２０）；②ｃ－ｅｒｂＢ２基因在宫颈癌中的扩增率为７３．３％（１１／１５），５例伴有重排；③ｃ－ｍｙｃ基因在宫颈癌中的扩增率为９１．７％（１１／１２）；④ＨＰＶ１６Ｅ６／Ｅ７为引物的ＰＣＲ检测结果，宫颈癌中的阳性率为８０．５％（３３／４１）；⑤１２例宫颈癌中未发现Ｐ５８、Ｒｂ基因缺失。上述多基因致癌机理的研究表明，人宫颈癌中Ｈａ－ｒａｓ、ｃ－ｍｙｃ、ｃ－ｅｒｂＢ２经点突变、扩增、重排而被激活，在癌变中起着协同致癌作用。ＨＰＶ１６基因的整合可能启动ｃ－ｍｙｃ，为癌变的起始因素，而Ｈａ－ｒａｓ、ｃ－ｅｒｂＢ２的基因改变可能为中、晚期事件，抑癌基因Ｐ５３、Ｒｂ的作用尚需进一步研究。
The alterations of multiple genes andtheir carcinogenic mechanism in cervical carcinomawere studies by molecular hybridization,PCR andPCR-ASO techaniques. The G→T point mutation inthe 12th coden of Ha-ras was detected in cervical carci-nomas with mutation frequency of 18.2%(8/44),andthe amplification rate of Ha-ras gene was 45%(9/20).The c-erb B2 was amplified 3-30 fold with an amplifica-tion rate of73.3%(11/15)in cervical carcinomas and5 cancerous samples showed gene rearrangement.Theelevated copies of c-myc gene with amplification rate of91.7%(11/12)were observed in cervical carcinomas.The study of HPV16 viral gene showed that the exis-tence of HPV16 DNA seauence was Dositively associat-ed whth c-myc gene amplification in cervical canceroussamples. The p53 and Rb tumor suppressor genes ab-sence of deletion were observed in the 12 specimens ofcervical carcinorna investigated. As mentioned above,the study on alteration and carcinogenic mechanism ofmultiple genes indicated that 3 oncogenes and HPV16viral gene were activated or integrated throygh differ-ent mechanisms and they played roles in co-carcino-genesis. The integration of HPV16 gene might promotethe c-myc gene at the carly stage in carcinogenesis ofcervical carcinoma, while the alteration of Ha-ras andc-erb B2 gene might be rniddle-late event. As for theroles of the p53 and Rb tumor suppresor gene in cervi-cal carcinoRenesis need further researches.
出处
《华西医科大学学报》
CSCD
1996年第1期5-9,共5页
Journal of West China University of Medical Sciences
基金
国家自然科学基金
关键词
宫颈癌
癌基因
病毒癌基因
抑癌基因
致癌机理
Cervical carcinoma Oncogenes Viral oncogene Tumor suppressor gene Carcinogenic mechanism of multiple genesThe Project Supported by National Natural Science Foundation of China
