title: Depletion of the cdk inhibitor p16INK4a differentially affects proliferation of established cervical carcinoma cells.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute for Biomedical Aging Research of Innsbruck University, Innsbruck, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pauck
authors.forename: Barbara
authors.initials: B
authors.lastname: Lener
authors.forename: Monika
authors.initials: M
authors.lastname: Hoell
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaiser
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: Werner
authors.initials: W
authors.lastname: Zwerschke
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050725:Papillomavirus E7 Proteins