A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma

Oncogene. 1996 Oct 17;13(8):1701-7.

Abstract

The proto-oncogene c-erbB-2 is overexpressed in 25-30% of breast cancers through increased transcription and amplification of the gene. We have previously described a factor, OB2-1 which upregulates c-erbB-2 transcription and which is closely related to the developmentally regulated transcription factor, AP-2. Further analysis of affinity purified OB2-1 has now shown that it is in fact a combination of proteins from three AP-2-related genes, the previously described AP-2alpha gene and two new human family members, AP-2beta and AP-2gamma whose cloning and characterisation are described here. All three AP-2 proteins show a high degree of homology and are capable of binding to the c-erbB-2 promoter as homo- or heterodimers. The three proteins can also activate a c-erbB-2 reporter construct, but AP-2alpha and AP-2gamma are 3-4 times more active in this regard than AP-2beta. In addition both AP-2alpha and AP-2gamma are expressed at elevated levels in the majority of c-erbB-2 overexpressing mammary tumour lines examined. Mechanisms which may have led to the increased AP-2 levels in these cells are discussed.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, erbB-2*
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Sequence Homology, Amino Acid
  • Transcription Factor AP-2
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

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

Associated data

  • GENBANK/X95693
  • GENBANK/X95694