THE ONCOGENIC POTENTIAL OF HUMAN PAPILLOMAVIRUS

人乳头状病毒的致癌潜力

• 批准号: 6236842
• 负责人: JAMES K. MCDOUGALL
• 金额: $ 26.54万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236842
• 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“高危”人类 乳头瘤病毒16型和18型启动一个多步骤的过程， 肛门生殖器癌，但不足以诱导 恶性肿瘤需要病毒E6/E7癌基因的持续表达 持续的细胞增殖，但其他变化引起的遗传 不稳定性也是完成恶性肿瘤途径所必需的。 我们将使用比较基因组杂交（CGH）和染色体 显微切割，以集中在染色体区域， 缺失或扩增以鉴定肿瘤抑制基因 意义重大来自宫颈癌档案标本的DNA， 流行病学研究中获得的其他肛门生殖器癌（项目 3)将用于等位基因型分析，探针用于基因座作图， 通过CGH或用已知或推定的染色体区域的探针鉴定的染色体区域 肿瘤抑制基因中微卫星不稳定性的普遍性 将研究肛门生殖器肿瘤，因为这些肿瘤的不稳定性 在许多肿瘤类型中已经观察到序列作为肿瘤发生的指示物。 突变子表型导致遗传错误。除了检查 遗传不稳定性对肿瘤进展的影响，我们将研究 细胞凋亡抑制剂的作用，因为这种抑制也可能影响 肿瘤的进展是细胞的持续增殖， 否则通过凋亡被消除。