A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma.
1701 - 1707.
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-2 alpha gene and two new human family members, AP-2 beta and AP-2 gamma 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-2 alpha and AP-2 gamma are 3-4 times more active in this regard than AP-2 beta. In addition both AP-2 alpha and AP-2 gamma 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.
|Title:||A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma|
|Keywords:||c-erbB-2, AP-2, transcription, mammary carcinoma, TRANSCRIPTION FACTOR AP-2, POSITIVE BREAST-CANCER, RNA POLYMERASE-II, NEU ONCOGENE, DNA-BINDING, RECEPTOR, OVEREXPRESSION, ACTIVATION, AMPLIFICATION, EMBRYOGENESIS|
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