ENHANCED DEGRADATION OF P53 PROTEIN IN HPV-6 AND BPV-1 E6-IMMORTALIZED HUMAN MAMMARY EPITHELIAL-CELLS
ENHANCED DEGRADATION OF P53 PROTEIN IN HPV-6 AND BPV-1 E6-IMMORTALIZED HUMAN MAMMARY EPITHELIAL-CELLS
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DOI：
10.1002/j.1460-2075.1993.tb05833.x
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发表时间：
1993-05-01
期刊：
影响因子：
11.4
通讯作者：
ANDROPHY, EJ
中科院分区：
文献类型：
--
作者：
BAND, V;DALAL, S;ANDROPHY, EJ
人类乳头瘤病毒(HPV)-16的E6基因可以有效地使正常的乳腺上皮细胞永生化，HPV-16是一种通常与宫颈癌有关的病毒。令人惊讶的是，将宫颈癌中罕见的HPV-6或牛乳头瘤病毒(BPV)-1的E6基因导入正常乳腺细胞，导致了永生细胞系的产生。与HPV-16E6相比，HPV-6和BPV-1E6永生化细胞的建立效率较低，所需时间较长。这些HPV-6和BPV-1E6永生化细胞通过免疫沉淀显示P53蛋白水平显著降低。P53蛋白在正常乳腺上皮细胞中的半衰期约为3小时，而在所有E6永生化细胞中的半衰期均缩短至约15分钟。这些结果表明，高危和低危乳头状瘤病毒的E6基因都能使人乳腺上皮细胞永生化，并在体内诱导P53蛋白的显着降解。
Normal mammary epithelial cells are efficiently immortalized by the E6 gene of human papillomavirus (HPV)-16, a virus commonly associated with cervical cancers. Surprisingly, introduction of the E6 gene from HPV-6, which is rarely found in cervical cancer, or bovine papillomavirus (BPV)-1, into normal mammary cells resulted in the generation of immortal cell tines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. While the half-life of p53 protein in normal mammary epithelial cells was approximately 3 h, it was reduced to approximately 15 min in all the E6-immortalized cells. These results demonstrate that the E6 genes of both high-risk and low-risk papilloma viruses immortalize human mammary epithelial cells and induce a marked degradation of p53 protein in vivo.