Abstract
Heat shock factor 1 (HSF1), the transcriptional activator of the heat shock genes, is increasingly implicated in cancer. We have shown that HSF1 binds to the corepressor metastasis-associated protein 1 (MTA1) in vitro and in human breast carcinoma samples. HSF1-MTA1 complex formation was strongly induced by the transforming ligand heregulin and complexes incorporated a number of additional proteins including histone deacetylases (HDAC1 and 2) and Mi2alpha, all components of the NuRD corepressor complex. These complexes were induced to assemble on the chromatin of MCF7 breast carcinoma cells and associated with the promoters of estrogen-responsive genes. Such HSF1 complexes participate in repression of estrogen-dependent transcription in breast carcinoma cells treated with heregulin and this effect was inhibited by MTA1 knockdown. Repression of estrogen-dependent transcription may contribute to the role of HSF1 in cancer.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Autoantigens / genetics
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Autoantigens / metabolism
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Chromatin / metabolism
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Chromatin Immunoprecipitation
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DNA Helicases / genetics
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DNA Helicases / metabolism
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DNA-Binding Proteins / physiology*
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Estrogens / pharmacology*
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Gene Expression Regulation, Neoplastic
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Heat Shock Transcription Factors
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylase Inhibitors
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Humans
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Immunoenzyme Techniques
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Neuregulin-1 / pharmacology
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Promoter Regions, Genetic
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Trans-Activators
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Transcription Factors / physiology*
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Transcription, Genetic*
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Tumor Cells, Cultured
Substances
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Autoantigens
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CHD4 protein, human
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Chromatin
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DNA-Binding Proteins
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Estrogens
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HSF1 protein, human
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Heat Shock Transcription Factors
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Histone Deacetylase Inhibitors
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Hsf1 protein, mouse
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MTA1 protein, human
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Neuregulin-1
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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HDAC1 protein, human
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Hdac2 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Adenosine Triphosphatases
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DNA Helicases