INHIBITION OF CERVICAL-CARCINOMA CELL-LINE PROLIFERATION BY THE INTRODUCTION OF A BOVINE PAPILLOMAVIRUS REGULATORY GENE
INHIBITION OF CERVICAL-CARCINOMA CELL-LINE PROLIFERATION BY THE INTRODUCTION OF A BOVINE PAPILLOMAVIRUS REGULATORY GENE
复制标题
DOI：
10.1128/jvi.67.7.3720-3729.1993
复制
发表时间：
1993-07-01
影响因子：
5.4
通讯作者：
DIMAIO, D
中科院分区：
文献类型：
--
作者：
HWANG, ES;RIESE, DJ;DIMAIO, D
人乳头瘤病毒 (HPV) E6 和 E7 癌基因在绝大多数人类宫颈癌中表达，而病毒 E2 调节基因通常在这些癌症中被破坏。为了研究乳头瘤病毒 E2 基因在宫颈癌发生和维持中的作用，通过感染高滴度的基于猿猴病毒 40 的重组病毒，将牛乳头瘤病毒 (BPV) E2 基因快速导入宫颈癌细胞系。 HeLa、C-4I 和 MS751 细胞中 BFV E2 蛋白的表达会特异性抑制 HPV 18 型 (HPV18) E6 和 E7 基因的表达，并抑制细胞生长。 HeLa 细胞中 HPV 基因表达几乎完全消失，其增殖受到显着且快速的抑制，这似乎很大程度上是细胞周期从 G1 期到 S 期进展受阻的结果。 HeLa 细胞中 HPV18 基因表达的丧失还伴随着细胞 p53 肿瘤抑制蛋白水平的显着增加，这显然是废除 HPV18 E6 介导的 p53 不稳定的结果。 HT-3 细胞（一种不含可检测到的 HPV DNA 的人宫颈癌细胞系）的增殖也受到 E2 表达的抑制，而另两种不含 HPV DNA 的上皮细胞系则不受抑制。因此，许多宫颈癌细胞系对E2蛋白的生长抑制非常敏感。尽管 BPV E2 介导的 HPV18 E6 和 E7 表达抑制可能有助于某些宫颈癌细胞系的生长抑制，但 BPV E2 蛋白似乎也发挥生长抑制作用，该作用与其对 HPV 基因表达的影响无关。
Human papillomavirus (HPV) E6 and E7 oncogenes are expressed in the great majority of human cervical carcinomas, whereas the viral E2 regulatory gene is usually disrupted in these cancers. To investigate the roles of the papillomavirus E2 genes in the development and maintenance of cervical carcinoma, the bovine papillomavirus (BPV) E2 gene was acutely introduced into cervical carcinoma cell lines by infection with high-titer stocks of simian virus 40-based recombinant viruses. Expression of the BFV E2 protein in HeLa, C-4I, and MS751 cells results in specific inhibition of the expression of the resident HPV type 18 (HPV18) E6 and E7 genes and in inhibition of cell growth. HeLa cells, in which HPV gene expression is nearly completely abolished, undergo a dramatic and rapid inhibition of proliferation, which appears to be largely a consequence of a block in progression from the G1 to the S phase of the cell cycle. Loss of HPV18 gene expression in HeLa cells is also accompanied by a marked increase in the level of the cellular p53 tumor suppressor protein, apparently as a consequence of abrogation of HPV18 E6-mediated destabilization of p53. The proliferation of HT-3 cells, a human cervical carcinoma cell line devoid of detectable HPV DNA, is also inhibited by E2 expression, whereas two other epithelial cell lines that do not contain HPV DNA are not inhibited. Thus, a number of cervical carcinoma cell lines are remarkably sensitive to growth inhibition by the E2 protein. Although BPV E2-mediated inhibition of HPV18 E6 and E7 expression may contribute to growth inhibition in some of the cervical carcinoma cell lines, the BPV E2 protein also appears to exert a growth-inhibitory effect that is independent of its effects on HPV gene expression.