Epidermal growth factor receptorrelated peptide inhibits growth of PC-3 prostate cancer cells

Interference with the activation of growth factor recep-tors, specifically epidermal growth factor receptor (EGFR), represents a promising strategy for the development of novel and selective anticancer therapies. We reported that EGFR-related peptide (ERRP), a recently isolated negative regulator of EGFR, could be a potential therapeutic agent for colorectal cancer. To determine whether ERRP could potentially be a therapeutic agent for prostate carcinoma, we examined the effect of recombinant ERRP on the growth of the prostate cancer cell line PC-3 in vitro. Events of the EGFR signal transduction pathways were also examined. ERRP caused a marked inhibition of cell growth in a dose- and time-dependent manner and also induced apoptosis. The latter was evidenced by increased number of apoptotic cells, activation of caspase-3, and cleavage of poly(ADP-ribose)polymerase. The transform-ing growth factor-a–induced stimulation of cell growth and activation of EGFR was also inhibited by ERRP. These changes were accompanied by a concomitant attenuation of activation of Akt and mitogen-activated protein kinases as well as basal and transforming growth factor-a– induced activation of nuclear factor-KB. Inhibition of EGFR activation by ERRP could be partly attributed to increased sequestration of EGFR ligands. In summary, our data show that ERRP inhibits the growth of prostate cancer cells by attenuating EGFR signaling processes. ERRP could poten-tially be an effective therapeutic agent for prostate cancer. [Mol Cancer Ther 2004;3(12):1615–21