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.
Hammarsten
Peter
P
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Rudolfsson
Stina Häggström
SH
Henriksson
Roger
R
Wikström
Pernilla
P
Bergh
Anders
A
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D000077156:Gefitinib; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; D013739:Testosterone; C483803:Egfr protein, rat; D066246:ErbB Receptors; D000077156:Gefitinib