The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3 cervical lesions

J Clin Invest. 1998 Apr 15;101(8):1687-92. doi: 10.1172/JCI1089.

Abstract

The cervical cellular transcription factors Brn-3a and Brn-3b have antagonistic effects on transcription of the human papilloma virus types 16 and 18 E6 and E7 oncogenes, with Brn-3a activating expression and Brn-3b repressing it. We therefore measured expression of Brn-3a and Brn-3b mRNAs in biopsies from 16 women with no detectable cervical abnormality, and in 14 women with cervical intraepithelial neoplasia grade 3 (CIN3) lesions. Although the mean level of Brn-3b expression was similar in both groups, the mean level of Brn-3a expression was over 300-fold higher in the CIN3 samples when compared with normals. Elevated expression of Brn-3a was also detected in 16 histologically normal regions of the cervix adjacent to the CIN3 lesions, indicating that elevation of Brn-3a levels is not confined to the lesion in women with CIN3, and is thus not a consequence of the oncogenic process. The elevated levels of Brn-3a in the CIN3 patient samples, together with the activating effect of Brn-3a on HPV-16 and -18 oncogene expression, suggest that induction of this factor is involved in activating HPV-16 and -18 oncogene expression in the cervix, and hence in the production of cervical cancers induced by HPV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Case-Control Studies
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Genes, Viral
  • Humans
  • Oncogenes
  • Papillomaviridae / genetics
  • Papillomaviridae / pathogenicity*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3A
  • Transcription Factor Brn-3B
  • Transcription Factors / genetics*
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / virology*

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • POU4F1 protein, human
  • POU4F2 protein, human
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3A
  • Transcription Factor Brn-3B
  • Transcription Factors