Post-transcriptional induction of p21cip1 protein in condylomata and dysplasias is inversely related to human papillomavirus activities

Am J Pathol. 1998 Apr;152(4):1015-24.

Abstract

Infections of the genital and oral epithelia by human papillomaviruses cause condylomata, papillomas, and squamous intraepithelial neoplasms, some of which can progress to invasive cancers. We describe an induction of p21cip1/WAF1/sdi1 protein in a fraction of the spinous cells in benign lesions and in cervical intraepithelial neoplasia grades I and II. The induction appears to be post-transcriptional and independent of p53. p21cip1 antigen-positive cells were sporadic in cervical intraepithelial neoplasia III and rare and focal in carcinomas. In contrast, p21cip1 protein was below or at the threshold of detection in the differentiated cells of normal squamous epithelia from different body sites despite an up-regulation of p21cip1 RNA. In cervical intraepithelial neoplasias from patients who were also positive for the human immunodeficiency virus, there was an additional increase in p21cip1 RNA in the upper spinous cells without concomitant p21cip1 protein induction. A consistent inverse relationship was observed between the p21cip1 protein induction and abundant human papillomavirus DNA and RNAs. We propose that p21cip1 protein induction is a novel host response that inhibits viral DNA replication and thus prevents elevated viral transcription. This hypothesis can partly account for the heterogeneity and the differentiation-dependent viral activities commonly observed in benign human papillomavirus lesions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Cervical Intraepithelial Neoplasia / metabolism
  • Condylomata Acuminata / metabolism*
  • Condylomata Acuminata / virology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • DNA, Viral / analysis
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Laryngeal Neoplasms / metabolism
  • Male
  • Papilloma / metabolism*
  • Papilloma / virology
  • Papillomaviridae / genetics
  • Papillomavirus Infections / metabolism*
  • Penile Neoplasms / metabolism
  • RNA, Viral / analysis
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Virus Infections / metabolism*
  • Vaginal Neoplasms / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Viral
  • RNA, Viral
  • Tumor Suppressor Protein p53