THE ONCOGENIC POTENTIAL OF HUMAN PAPILLOMAVIRUS

人乳头状病毒的致癌潜力

• 批准号: 6102321
• 负责人: JAMES K. MCDOUGALL
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102321
• 关键词: apoptosis; carcinoma; cell line; cervix neoplasms; comparative genomic hybridization; complementary DNA; gene expression; genetic library; growth inhibitors; human papillomavirus; human tissue; in situ hybridization; major histocompatibility complex; metastasis; neoplasm /cancer invasiveness; nicotine; oncogenes; rectum neoplasms; telomere; tissue /cell culture; tumor suppressor genes; viral carcinogenesis

This project is based on the hypothesis that the "high-risk" human papillomavirus types 16 and 18 initiate a multi-step process that can lead to anogenital carcinoma but are not sufficient for the induction of malignancy. Continued expression of the viral E6/E7 oncogenes is required for continued cell proliferation but other changes resulting from genetic instability are also required for completion of the pathway to malignancy. We will use comparative genomic hybridization (CGH) and chromosome microdissection to focus on chromosomal regions subject to non-random deletion or amplification in an effort to identify tumor suppressor genes of significance. DNA from archival specimens of cervical carcinoma and other anogenital carcinomas acquired in the epidemiologic studies (Project 3) will be used in allelotype analyses with probes for loci mapping in chromosome regions identified by CGH or with probes for known or putative tumor suppressor genes. The prevalence of microsatellite instability in anogenital tumors will be investigated, since instability of these sequences has been observed in many tumor types as an indicator of a mutator phenotype leading to genetic errors. As well as examining the effects of genetic instability on tumor progression, we will examine the effects of inhibitors of apoptosis, since such inhibition may also affect tumor progression by the continued proliferation of cells that would otherwise be eliminated through apoptosis.

这个项目是基于这样一个假设，即“高风险”的人类 16型和18型乳头瘤病毒启动了一个多步骤的过程，可以导致 对肛门生殖器癌，但不足以诱导 恶毒。病毒E6/E7癌基因需要持续表达 持续的细胞增殖，但其他由基因引起的变化 不稳定也是完成致癌途径所必需的。 我们将使用比较基因组杂交(CGH)和染色体 聚焦于非随机染色体区域的显微切割 为了识别肿瘤抑制基因而进行的缺失或扩增 意义重大。从宫颈癌和子宫颈癌的档案标本中提取DNA 流行病学研究中获得的其他肛门生殖器癌(项目 3)将用于等位基因分析，用探针进行基因座定位 用CGH或已知或推定的探针鉴定染色体区域 肿瘤抑制基因。中国人群中微卫星不稳定性的流行 将对肛门生殖器肿瘤进行调查，因为这些肿瘤不稳定 序列已经在许多肿瘤类型中被观察到，作为一种指示 导致遗传错误的突变体表型。以及检查 遗传不稳定性对肿瘤进展的影响，我们将研究 细胞凋亡抑制物的作用，因为这种抑制也可能影响 通过细胞的持续增殖而导致的肿瘤进展 否则就会通过细胞凋亡被消灭。