Band V, De Caprio J A, Delmolino L, Kulesa V, Sager R
Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
J Virol. 1991 Dec;65(12):6671-6. doi: 10.1128/JVI.65.12.6671-6676.1991.
We have shown previously that introduction of the human papillomavirus type 16 (HPV16) or HPV18 genome into human mammary epithelial cells induces their immortalization. These immortalized cells have reduced growth factor requirements. We report here that transfection with a single HPV16 gene E6 is sufficient to immortalize these cells and reduce their growth factor requirements. The RB protein is normal in these cells, but the p53 protein is sharply reduced, as shown by immunoprecipitation with anti-p53 antibody (pAB 421). We infer that the E6 protein reduces the p53 protein perhaps by signalling its destruction by the ubiquitin system. The HPV-transforming gene E7 was unable to immortalize human mammary epithelial cells. Thus, cell-specific factors may determine which viral oncogene plays a major role in oncogenesis.
我们之前已经表明,将人乳头瘤病毒16型(HPV16)或HPV18基因组导入人乳腺上皮细胞会诱导其永生化。这些永生化细胞对生长因子的需求降低。我们在此报告,用单个HPV16基因E6进行转染足以使这些细胞永生化并降低其对生长因子的需求。这些细胞中的RB蛋白正常,但p53蛋白急剧减少,如用抗p53抗体(pAB 421)进行免疫沉淀所示。我们推断E6蛋白可能通过泛素系统发出信号使其降解,从而降低p53蛋白水平。HPV转化基因E7无法使人乳腺上皮细胞永生化。因此,细胞特异性因子可能决定哪种病毒癌基因在肿瘤发生中起主要作用。