Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras

  • Berger, Kristi L.
  • Barriga, Felicia
  • Lace, Michael J.
  • Turek, Lubomir P.
  • Zamba, Gideon J.
  • Domann, Frederick E.
  • Lee, John H.
  • Klingelhutz, Aloysius J.
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Publication date
December 2006
Publisher
Elsevier Inc.
ISSN
0042-6822
Citation count (estimate)
12

Abstract

AbstractRas expression in human epithelial cells with integrated HPV genomes has been shown to cause tumorigenic transformation. The effects of Ras in cells representing early stage HPV-associated disease (i.e., when HPV is extrachromosomal and the oncogenes are under control of native promoters) have not been examined. Here, we used human cervical keratinocyte cell lines containing stably replicating extrachromosomal HPV-16 and present the novel finding that these cells resist transformation by oncogenic H-Ras. Ras expression consistently diminished anchorage-independent growth (AI), reduced E6 and E7 expression, and caused p53 induction in these cells. Conversely, AI was enhanced or maintained in Ras-transduced cervical cells that were im...

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