Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1

Oncogene volume 27, pages 1886–1893 (2008)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Bewick M, Chadderton T, Conlon M, Lafrenie R, Morris D, Stewart D et al. (1999). Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support. Bone Marrow Transplant 24: 377–384.

    Article  CAS  PubMed  Google Scholar 

  • Bowen NJ, Fujita N, Kajita M, Wade PA . (2004). Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677: 52–57.

    Article  CAS  PubMed  Google Scholar 

  • Cahill CM, Waterman WR, Auron PE, Calderwood SK . (1996). Transcriptional repression of the prointerleukin1B gene by heat shock factor 1. J Biol Chem 271: 24874–24879.

    CAS  PubMed  Google Scholar 

  • Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR . (2006). Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31: 164–172.

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Xie Y, Stevenson MA, Auron PE, Calderwood SK . (1997). Heat shock factor 1 represses ras-induced transcriptional activation of the c-fos gene. J Biol Chem 272: 26803–26806.

    Article  CAS  PubMed  Google Scholar 

  • Ciocca DR, Calderwood SK . (2005). Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10: 86–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gago G, Kurth D, Diacovich L, Tsai SC, Gramajo H . (2006). Biochemical and structural characterization of an essential acyl coenzyme a carboxylase from mycobacterium tuberculosis. J Bacteriol 188: 477–486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoang AT, Huang J, Rudra-Ganguly N, Zheng J, Powell WC, Rabindran SK et al. (2000). A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma. Am J Pathol 156: 857–864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones EL, Zhao MJ, Stevenson MA, Calderwood SK . (2004). The 70 kilodalton heat shock protein is an inhibitor of apoptosis in cancer. Int J Hyperthermia 20: 835–849.

    Article  CAS  PubMed  Google Scholar 

  • Khaleque MA, Bharti A, Sawyer D, Benjamin IJ, Stevenson MA, Calderwood SK . (2005). Induction of heat shock proteins by heregulin beta1 leads to protection from apoptosis and anchorage-independent growth. Oncogene 24: 6564–6573.

    Article  CAS  PubMed  Google Scholar 

  • Kumar R, Wang RA, Bagheri-Yarmand R . (2003). Emerging roles of MTA family members in human cancers. Semin Oncol 30: 30–37.

    Article  CAS  PubMed  Google Scholar 

  • Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M et al. (2001). Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3: 30–37.

    Article  CAS  PubMed  Google Scholar 

  • Mosser DD, Morimoto RI . (2004). Molecular chaperones and the stress of oncogenesis. Oncogene 23: 2907–2918.

    Article  CAS  PubMed  Google Scholar 

  • Neubauer BL, McNulty AM, Chedid M, Chen K, Goode RL, Johnson MA et al. (2003). The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model. Cancer Res 63: 6056–6062.

    CAS  PubMed  Google Scholar 

  • Tang D, Khaleque AA, Jones ER, Theriault JR, Stevenson MA, Calderwood SK . (2005). Expression of heat shock proteins and HSP messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 10: 46–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toh Y, Kuninaka S, Endo K, Oshiro T, Ikeda Y, Nakashima H et al. (2000). Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1. J Exp Clin Cancer Res 19: 105–111.

    CAS  PubMed  Google Scholar 

  • Wang X, Grammatikakis N, Siganou A, Calderwood SK . (2003). Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1. Mol Cell Biol 23: 6013–6026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Grammatikakis N, Siganou A, Stevenson MA, Calderwood SK . (2004a). Interactions between extracellular signal-regulated protein kinase 1, 14-3-3epsilon, and heat shock factor 1 during stress. J Biol Chem 279: 49460–49469.

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Khaleque MA, Zhao MJ, Zhong R, Gaestel M, Calderwood SK . (2006). Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding. J Biol Chem 281: 782–791.

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Theriault JR, He H, Gong J, Calderwood SK . (2004b). Expression of a dominant negative heat shock factor-1 construct inhibits aneuploidy in prostate carcinoma cells. J Biol Chem 279: 32651–32659.

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK . (2002). Heat shock factor 1 represses transcription of the IL-1b gene through physical interaction with nuclear factor of interleukin 6. J Biol Chem 277: 11802–11810.

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Zhong R, Chen C, Calderwood SK . (2003). Heat Shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes. J Biol Chem 278: 4687–4698.

    Article  CAS  PubMed  Google Scholar 

  • Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W . (1998). NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2: 851–861.

    Article  CAS  PubMed  Google Scholar 

  • Yao YL, Yang WM . (2003). The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity. J Biol Chem 278: 42560–42568.

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Author notes

  1. M A Khaleque and A Bharti: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    M A Khaleque, P J Gray & S K Calderwood

  2. Department of Biochemistry, North South University, Dhaka, Bangladesh

    M A Khaleque

  3. Department of Medicine, Boston University, Mendoza, Argentina

    A Bharti, J Gong, V Sachdev & S K Calderwood

  4. Laboratory of Oncology, Institute for Experimental Medicine and Biology of Cuyo, Mendoza, Argentina

    D R Ciocca, A Stati & M Fanelli

Authors
  1. M A Khaleque
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Bharti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P J Gray
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V Sachdev
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D R Ciocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Stati
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Fanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S K Calderwood
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S K Calderwood.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210834

Keywords

This article is cited by

Search

Advanced search

Quick links