title: Epidermal growth factor receptor-related peptide inhibits growth of PC-3 prostate cancer cells.
abstract: Interference with the activation of growth factor receptors, 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 transforming growth factor-alpha-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-alpha-induced activation of nuclear factor-kappaB. 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 potentially be an effective therapeutic agent for prostate cancer.
authors.affiliation: Departments of Internal Medicine and Pathology, John D. Dingell Veterans Affairs Medical Center, Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Dorota J
authors.initials: DJ
authors.lastname: Marciniak
authors.forename: Arun K
authors.initials: AK
authors.lastname: Rishi
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Adhip P N
authors.initials: AP
authors.lastname: Majumdar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D006023:Glycoproteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D016211:Transforming Growth Factor alpha; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases