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

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 beta1 (HRGbeta1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRGbeta1. HSP expression is induced through a cascade response initiated by HRGbeta1 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 HRGbeta1, indicating a role for HSF1 in this tumorigenic pathway.