Vieira K B, Goldstein D J, Villa L L
Ludwig Institute for Cancer Research, Sao Paulo, Brazil.
Cancer Res. 1996 May 15;56(10):2452-7.
We have shown that normal and human papillomavirus (HPV) type 16 immortalized human foreskin keratinocytes are growth inhibited by tumor necrosis factor alpha (TNF-alpha), whereas HPV-18- and SV40-immortalized keratinocytes are resistant to this cytokine (1). In this report, we investigated the expression of mitotic regulatory proteins, such as cyclin A, cyclin B, and p34cdc2. After exposure to TNF-alpha, normal and HPV-16-immortalized cells exhibited a dramatic decrease in the expression of these proteins. In contrast, no alteration in the levels of these proteins was observed after treatment of the resistant cell lines, as well as two HPV-positive cervical carcinoma cell lines. Expression of cyclin E does not seem to be modulated by TNF-alpha in any of the cells tested. On the other hand, cyclin D1, expression is slightly increased in normal keratinocytes and in the HPV-16-immortalized cells, whereas no alteration was observed in the HPV-18-transfected cells. The phosphorylation state of pRb correlated with cell growth; sensitive cells, which accumulate in G0-G1, after exposure to TNF-alpha, exhibited an accumulation of hypophosphorylated pRb, whereas no effect on pRb phosphorylation was observed for HPV-18-immortalized cells. These results clearly correlate with TNF-alpha-induced growth arrest in G0-G1.
我们已经表明，正常和人乳头瘤病毒（HPV）16型永生化的人包皮角质形成细胞受到肿瘤坏死因子α（TNF-α）的生长抑制，而HPV-18和SV40永生化的角质形成细胞对这种细胞因子具有抗性（1）。在本报告中，我们研究了有丝分裂调节蛋白的表达，如细胞周期蛋白A、细胞周期蛋白B和p34cdc2。暴露于TNF-α后，正常和HPV-16永生化细胞中这些蛋白的表达显著下降。相比之下，在抗性细胞系以及两种HPV阳性宫颈癌细胞系处理后，未观察到这些蛋白水平的改变。在任何测试的细胞中，细胞周期蛋白E的表达似乎都不受TNF-α的调节。另一方面，细胞周期蛋白D1在正常角质形成细胞和HPV-16永生化细胞中的表达略有增加，而在HPV-18转染细胞中未观察到改变。pRb的磷酸化状态与细胞生长相关；敏感细胞在暴露于TNF-α后在G0-G1期积累，表现出低磷酸化pRb的积累，而HPV-18永生化细胞中未观察到对pRb磷酸化的影响。这些结果与TNF-α诱导的G0-G1期生长停滞明显相关。
