A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma.
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.
Gene Transcription Laboratory, ICRF Oncology Unit, Hammersmith Hospital, London, UK.
J M
JM
Bosher
N F
NF
Totty
J J
JJ
Hsuan
T
T
Williams
H C
HC
Hurst
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018734:Genes, erbB-2; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D017386:Sequence Homology, Amino Acid; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C493673:TFAP2A protein, human; C493677:TFAP2B protein, human; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors