ABSTRACT

Infections with high-risk human papillomaviruses (hrHPV) contribute to cervical carcinoma. The cdk inhibitor and tumor suppressor p16^INK4A is consistently upregulated in cervical carcinoma cells for reasons that are poorly understood. We report here that downregulation of p16^INK4A gene expression in three different cervical carcinoma cell lines reduced expression of the E7 oncogene, suggesting a positive feedback loop involving E7 and p16^INK4A. p16^INK4A depletion induced cellular senescence in HeLa but not CaSki and MS-751 cervical carcinoma cells.

IMPORTANCE This study demonstrates that the cdk inhibitor p16^INK4A, 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 p16^INK4A induces senescence in HeLa but not CaSki or MS-751 cervical carcinoma cells.