IN VITRO STUDIES OF HUMAN MESOTHELIAL CELL CARCINOGENESIS

人间皮细胞致癌的体外研究

• 批准号: 3874756
• 负责人: B I GERWIN
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874756
• 关键词: asbestos; athymic mouse; biological signal transduction; carcinogenesis; cell growth regulation; cellular oncology; mesothelioma; mitogens; neoplasm /cancer genetics; neoplastic cell; oncogenes; peptides; platelet derived growth factor; retinoblastoma; simian virus 40; tissue /cell culture; transforming growth factors; viral carcinogenesis; virus antigen

The human mesothelioma cell lines established by this laboratory represent a sizeable number of examples of this relatively rare tumor type. Accordingly, these cell lines have been analyzed for the status of the retinoblastoma gene, the K- and H-ras genes and the p53 gene. The findings indicate that, while involvement of the retinoblastoma gene in this disease is unlikely, mutations in the p53 gene may occur. Utilizing the immortalized, nontumorigenic human mesothelial cell line, MET-5A, developed at LHC, we have tested the tumorigenic potential of EJ-ras and the human platelet-derived growth factor (PDGF)-A and -B chain genes. The results to date indicate that overexpression of both mutated ras and the PDGF-A chain can convert this cell line to tumorigenicity. It is of interest that the tumors induced by these different genes differ both with respect to their growth rate in vivo and their histopathological type, resembling either the epithelial or spindeloid type of human mesothelioma.

本实验室建立的人间皮瘤细胞系代表 这种相对罕见的肿瘤类型有相当多的例子。 因此，对这些细胞系的状态进行了分析 视网膜母细胞瘤基因、K-和H-ras基因以及p53基因。研究结果 表明，虽然视网膜母细胞瘤基因参与这种疾病 不太可能，p53 基因可能会发生突变。利用 开发出永生化、非致瘤性人间皮细胞系 MET-5A 在 LHC，我们测试了 EJ-ras 和人类的致瘤潜力 血小板衍生生长因子 (PDGF)-A 和 -B 链基因。结果至 日期表明突变 ras 和 PDGF-A 链的过度表达 可以将该细胞系转化为致瘤性。有趣的是 由这些不同基因诱导的肿瘤在它们的方面有所不同 体内生长速率及其组织病理学类型，类似于 人类间皮瘤的上皮型或纺锤体型。