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 1 (HRG1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRG1. HSP expression is induced through a cascade response initiated by HRG1 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 HRG1, indicating a role for HSF1 in this tumorigenic pathway.