Inhibition of the epidermal growth factor receptor enhances castration-induced prostate involution and reduces testosterone-stimulated prostate growth in adult rats

BACKGROUND The epidermal growth factor receptor (EGFR) mediates regulatory signals in the normal prostate, but the functional importance of this is unclear. METHODS Adult male rats were castrated, or castrated + treated with gefitinib (Iressa®, ZD1839), an EGFR tyrosine kinase inhibitor, for 3 days. Seven‐day castrated rats were treated with testosterone, or testosterone + gefitinib, for 3 days. RESULTS Both castration alone and testosterone treatment in castrated animals increased the mRNA and protein levels of EGFR and phospho‐EGFR in the ventral prostate. Inhibition of EGFR during castration and during testosterone‐stimulated prostate growth resulted in a decrease in total epithelial weight, epithelial cell proliferation, endothelial cell proliferation, and increased epithelial cell apoptosis. CONCLUSIONS This study suggests that increased EGFR signaling during castration mediates stimulatory effects balancing castration‐induced prostate regression, and that EGFR signaling is a necessary component in testosterone‐stimulated prostate growth. Prostate 67: 573–581, 2007. © 2007 Wiley‐Liss, Inc.