Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription

J Mol Med (Berl). 2001 Jun;79(5-6):314-20. doi: 10.1007/s001090100211.

Abstract

The AP-2 family of transcription factors consists of three known members, namely AP-2alpha, AP-2beta, and AP-2gamma. In experimental systems AP-2 factors possess tumor suppressor-like activities, and alterations in the AP-2 expression pattern have been described for some tumor entities. In addition, AP-2 has been implicated in the transcriptional control of human papillomaviruses (HPVs). We investigated here the expression pattern of AP-2alpha, AP-2beta, and AP-2gamma, as well as that of the cellular AP-2 target gene c-erbB-2, in a series of cervical cancer cell lines. In addition, we analyzed the influence of AP-2 factors on the activity of the HPV16 and HPV18 E6/E7 oncogene promoter. We found that, with the exception of HPV-negative C33A cells, all investigated cervical cancer cell lines expressed all three AP-2 family members, although at varying levels. No linear correlation between AP-2 and c-erbB-2 levels was observed. Although AP-2alpha, AP-2beta, and AP-2gamma can activate the c-erbB-2 promoter in reporter gene assays, they do not stimulate the HPV16 or HPV18 E6/E7 promoter. These results indicate that, although a rare event, loss of AP-2 expression occurs in cervical cancer cells. Moreover, AP-2alpha, AP-2beta, and AP-2gamma are neither sufficient nor required to activate the viral E6/E7 promoter.

MeSH terms

  • Antibody Specificity
  • Blotting, Western
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Viral / genetics*
  • Genes, Viral / genetics
  • Genes, erbB-2 / genetics
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Mutation / genetics
  • Oncogenes / genetics*
  • Papillomaviridae / genetics*
  • Promoter Regions, Genetic / genetics
  • Transcription Factor AP-2
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics
  • Transfection
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / virology*

Substances

  • DNA-Binding Proteins
  • TFAP2A protein, human
  • TFAP2B protein, human
  • TFAP2C protein, human
  • Transcription Factor AP-2
  • Transcription Factors