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 Mi2α, 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.
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Acknowledgements
We thank Dr Yasushi Toh for the pBJ-Myc-MTA1 expression plasmid, Dr Michael M Wang for pERE-Luc and Dr Ivor J Benjamin for hsf1 wild-type and null MEFs. This study was supported by NIH grant CA077465.
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Khaleque, M., Bharti, A., Gong, J. et al. Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1. Oncogene 27, 1886–1893 (2008). https://doi.org/10.1038/sj.onc.1210834
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DOI: https://doi.org/10.1038/sj.onc.1210834
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