Institute for Biomedical Aging Research of Innsbruck University, Innsbruck, Austria.
J Virol. 2014 May;88(10):5256-62. doi: 10.1128/JVI.03817-13. Epub 2014 Mar 5.
Infections with high-risk human papillomaviruses (hrHPV) contribute to cervical carcinoma. The cdk inhibitor and tumor suppressor p16INK4A is consistently upregulated in cervical carcinoma cells for reasons that are poorly understood. We report here that downregulation of p16INK4A gene expression in three different cervical carcinoma cell lines reduced expression of the E7 oncogene, suggesting a positive feedback loop involving E7 and p16INK4A. p16INK4A depletion induced cellular senescence in HeLa but not CaSki and MS-751 cervical carcinoma cells.
This study demonstrates that the cdk inhibitor p16INK4A, frequently used as surrogate marker for transforming infections by human papillomaviruses of the high-risk group, is required for high-level expression of the E7 oncoproteins of HPV-16, HPV-18, and HPV-45 in cervical carcinoma cells. It is also demonstrated that depletion of p16INK4A induces senescence in HeLa but not CaSki or MS-751 cervical carcinoma cells.
高危型人乳头瘤病毒（hrHPV）感染可导致宫颈癌。细胞周期蛋白依赖性激酶抑制剂和肿瘤抑制因子 p16INK4A 在宫颈癌细胞中持续上调，其原因尚不清楚。我们在此报告，在三种不同的宫颈癌细胞系中下调 p16INK4A 基因表达会降低 E7 癌基因的表达，表明涉及 E7 和 p16INK4A 的正反馈回路。p16INK4A 耗竭诱导 HeLa 细胞发生衰老，但 CaSki 和 MS-751 宫颈癌细胞不会发生衰老。
这项研究表明，细胞周期蛋白依赖性激酶抑制剂 p16INK4A 常被用作人乳头瘤病毒高危型转化感染的替代标志物，是 HPV-16、HPV-18 和 HPV-45 的 E7 癌蛋白在宫颈癌细胞中高水平表达所必需的。此外，还证明了 p16INK4A 的耗竭会诱导 HeLa 细胞发生衰老，但不会诱导 CaSki 或 MS-751 宫颈癌细胞发生衰老。
