Faculty Collaboration Database

Induction of heat shock proteins by heregulin beta1 leads to protection from apoptosis and anchorage-independent growth. Oncogene 2005 Sep 29;24(43):6564-73

Date

07/12/2005

Pubmed ID

16007186

DOI

10.1038/sj.onc.1208798

Scopus ID

2-s2.0-26944442444 (requires institutional sign-in at Scopus site)   91 Citations

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.

Author List

Khaleque MA, Bharti A, Sawyer D, Gong J, Benjamin IJ, Stevenson MA, Calderwood SK

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Cell Proliferation
DNA-Binding Proteins
Fibroblasts
Glycogen Synthase Kinase 3
Heat Shock Transcription Factors
Heat-Shock Proteins
Humans
Mice
Neuregulin-1
Oncogene Proteins v-erbB
Signal Transduction
Transcription Factors
Transcription, Genetic
Tumor Cells, Cultured
Tumor Stem Cell Assay