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Induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and anchorage-independent growth

Oncogene volume 24, pages 6564–6573 (2005)Cite this article

Abstract

Elevation of heat shock protein (HSP) levels is widespread in cancer and predicts a poor prognosis and resistance to therapy. We show that HSP elevation in tumor cells can be induced by the highly malignant factor heregulin β1 (HRGβ1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRGβ1. HSP expression is induced through a cascade response initiated by HRGβ1 binding to c-erbB receptors on the cell surface and which leads to the inhibition of intracellular HSF1 antagonist glycogen synthase kinase 3. HSF1 activated by this pathway plays a key role in the protection of cells from apoptosis and the mediation of anchorage independent growth by HRGβ1, indicating a role for HSF1 in this tumorigenic pathway.

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Acknowledgements

We thank Dr Rehan Ahmed (Dana Farber Cancer Institute) and Dr Jimmy R Theriault (Beth Israel Deaconess Medical Center) for expert assistance with the apoptosis assay. This work was supported by National Institutes of Health Grants CA47407, CA31303 and CA50642.

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Authors and Affiliations

  1. Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA

    Md Abdul Khaleque, Mary Ann Stevenson & Stuart K Calderwood

  2. Department of Medicine, Boston University School of Medicine, Boston, 02118, MA, USA

    Ajit Bharti, Douglas Sawyer, Jianlin Gong & Stuart K Calderwood

  3. Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, 84132, UT, USA

    Ivor J Benjamin

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  1. Md Abdul Khaleque
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Correspondence to Stuart K Calderwood.

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Khaleque, M., Bharti, A., Sawyer, D. et al. Induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and anchorage-independent growth. Oncogene 24, 6564–6573 (2005). https://doi.org/10.1038/sj.onc.1208798

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