Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation

作者: William C. Hahn , Scott K. Dessain , Mary W. Brooks , Jessie E. King , Brian Elenbaas

DOI: 10.1128/MCB.22.7.2111-2123.2002

关键词:

摘要: While it is clear that cancer arises from the accumulation of genetic mutations endow malignant cell with properties uncontrolled growth and proliferation, precise combinations program human tumor remain unknown. The study transforming proteins derived DNA viruses in experimental models transformation has provided fundamental insights into process transformation. We recently reported coexpression simian virus 40 (SV40) early region (ER), gene encoding telomerase catalytic subunit (hTERT), an oncogenic allele H-ras normal fibroblast, kidney epithelial, mammary epithelial cells converted these to a tumorigenic state. Here we show SV40 ER contributes presence hTERT by perturbing three intracellular pathways through actions large T antigen (LT) small t (ST). LT simultaneously disables retinoblastoma (pRB) p53 suppressor pathways; however, complete requires additional perturbation protein phosphatase 2A ST. Expression ST this setting stimulates permits anchorage-independent growth, confers increased resistance nutrient deprivation. Taken together, observations define elements required for begin delineate set whose disruption, aggregate, appears be necessary generate cells.

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