Investigation on protooncogenes in gynecologic malignancies

妇科恶性肿瘤中原癌基因的研究

基本信息

批准号：
62570763
负责人：
IWASAKA Tsuyoshi
金额：
$ 1.22万
依托单位：
佐賀医科大学
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Oncogenic potential of human papillomavirus (HPV) which is associated with occurrence of cervical carcinoma and mechanism of oncogenesis by this virus was investigated by transformation experiments in vitro. The results were obtained as follows. 1) Complete carcinogenesis can be mediated by HPV-16 or HPV-18 DNA under collaboration with other cofactors such as HSV-2.2) It is suggested that neoplastic transformation induced by HPV-18 DNA is based on "hit and run" oncogenesis. 3) HPV-16 or HPV-18 DNA can immortalize primary diploid cells and convert them to fully tumorigenic phenotype by repeating cell passage. 4) It has been experimentally proved that the difference in transforming potential exists between HPV 6/11 and HPV 16/18.5) Amplification and overexpression of c-myc oncogene was detected in transformed cells obtained by HPV-16 transfection. While overexpression of c-myc was detected in transformed cells induced by HPV-18 DNA, but no amplification was observed.On the other hand, de … More tection of HPV DNA and amplification or overexpression of protooncogenes was performed in cervical intraepithelial neoplasias (CIN) and invasive cervical carcinomas. The results were summarized as follows. 1) HPV DNA was detected in approximately 70% of a population with CIN by in situ hybridization. CIN II showed the highest incidence of positive HPV DNA(91%),and the positive ratio decreased in CIN III(56%). 2) Immunohistochemical study of paraffin-embedded specimens with monoclonal antibodies to oncogene products revealed that only some of cervical invasive carcinomas expressed c-myc protein, ras p21 or EGFR. 3) HPV DNA was detected in 46% of invasive cervical carcinomas by Southern blot hybridization. The percentage of patients with positive results for HPV 16/18 was 29%. However, it increased up to 58% by use of polymerase chain reaction(PCR), suggesting that there are many cervical cancer tissues in which a number of cells lack viral DNA. 4) Northern blot hybridization analysis revealed overexpression of c-myc mRNA in 30% of cervical invasive carcinomas although amplification of c-myc oncogene was detected in only one of invasive carcinomas. Less

人乳头瘤病毒（HPV）的致癌潜力与该病毒的宫颈癌的发生以及该病毒的肿瘤发生机制有关。结果如下。 1）在与其他辅助因子（例如HSV-2.2）合作的HPV-16或HPV-18 DNA可以介导完整的致癌作用，建议由HPV-18 DNA诱导的肿瘤转化基于“命中和运行”。 3）HPV-16或HPV-18 DNA可以使原代二倍体细胞永生，并通过重复细胞传递将其转换为完全致瘤的表型。 4）在实验上证明，在HPV 6/11和HPV 16/16/18.5之间存在转化电位的差异）在通过HPV-16转化获得的转化细胞中检测到了C-Myc癌基因的扩增和过表达。虽然在HPV-18 DNA诱导的转化细胞中检测到C-MYC的过表达，但未观察到放大。另一方面，在宫颈上皮内肿瘤（CIN）和入侵性颈部颈carc骨中，对HPV DNA的更多测试以及Protooncogenes的扩增或过表达进行了。结果总结如下。 1）通过原位杂交在大约70％的CIN人群中检测到HPV DNA。 CIN II显示出HPV阳性DNA的发病率最高（91％），CIN III的正比率降低（56％）。 2）对癌基产品单克隆抗体的石蜡包裹的标本的免疫组织化学研究表明，只有一些宫颈浸润性癌表达C-Myc蛋白Ras P21或EGFR。 3）通过Southern印迹杂交在46％的浸润性宫颈癌中检测到HPV DNA。 HPV 16/18阳性的患者百分比为29％。然而，通过使用聚合酶链反应（PCR），它增加了58％，这表明许多细胞缺乏病毒DNA的宫颈癌组织。 4）北印迹杂交分析表明，尽管仅在一种浸润性癌中检测到C-Myc癌基因的扩增，但在30％的宫颈浸润性癌中C-MYC mRNA过表达。较少的