Abstract
Germ-line mutations of the BRCA2 tumor suppressor gene greatly increase the risk of developing breast and ovarian cancers. Here, we show that wild-type BRCA2, but not a tumor-specific truncated mutant BRCA2, synergizes with the nuclear receptor coactivator p160 GRIP1 to enhance transcriptional activation by androgen receptor (AR). BRCA2 not only associates with AR and GRIP1 but also cooperates with both the histone acetyltransferase P/CAF and BRCA1 to enhance AR- and GRIP1-mediated transactivation. As such, BRCA2 can exert its tumor suppressor function, in part, by modulating androgen signaling, which has been shown to be antiproliferative in a subset of breast cancer cells and particularly implicated in male breast tumors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetyltransferases / metabolism*
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BRCA1 Protein / metabolism
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BRCA2 Protein / metabolism*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms, Male / genetics
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Breast Neoplasms, Male / metabolism
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Cell Cycle Proteins / metabolism
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Cell Line
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DNA Repair
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Female
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Genes, BRCA2
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Histone Acetyltransferases
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Humans
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Male
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Mutation
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Nuclear Receptor Coactivator 2
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Protein Structure, Tertiary
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism*
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Risk Factors
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Saccharomyces cerevisiae Proteins / metabolism*
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Sequence Deletion
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Signal Transduction
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Transcriptional Activation
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p300-CBP Transcription Factors
Substances
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BRCA1 Protein
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BRCA2 Protein
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Cell Cycle Proteins
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NCOA2 protein, human
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Nuclear Receptor Coactivator 2
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Receptors, Androgen
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor