Heregulin up-regulates heat shock protein-70 expression in breast cancer cells

The mechanism underlying the diverse functions of Heregulin-beta1 (HRG), a combinatorial ligand for human epidermal growth factor receptors 3 (HER3) and 4 (HER4), is not well understood but it is believed to involve induced changes in the expression of specific cellular gene products, their modification, or both. We performed differential display screening in cells grown in the presence or absence of HRG to identify genes whose expression may be modulated by HRG. Isolates from one cDNA clone were 100% identical to human heat shock protein-70 (Hsp70), a protein that functions as a molecular chaperone. We identified Hsp70 as one of the HRG-inducible gene products in human breast cancer cells. In addition, human breast tumor samples contained more Hsp70 protein than did samples from adjacent normal tissue. Because Hsp70 acts as a molecular chaperone with cell survival function, our findings suggest that stimulation of Hsp70 expression is a potential mechanism of protein redistribution in growth-factor-activated cells.