Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells.

摘要: Inactivation of epidermal growth factor receptor (EGFR) family members represents a promising strategy for the development selective therapies against epithelial cancers. Current anti-EGFR therapies, such as cetuximab (Erbitux), gefitinib (Iressa), or trastuzumab (Herceptin), target EGFR HER-2 but not both. Because solid tumors express different EGFRs, identification inhibitor(s), targeting multiple may provide therapeutic benefit to broader patient population. We have identified natural inhibitor EGFRs called EGFR-related protein (ERRP), 53 55 kDa that is present in most, if all, normal human cells. The colon (HCT-116, Caco2, and HT-29) breast (MDA-MB-468 SKBR-3) cancer cells expressing varying levels EGFR, HER-2, and/or HER-4 was inhibited by recombinant ERRP dose-dependent manner. In contrast, caused no inhibition mouse fibroblast cell lines (NIH-3T3, NIH-3T3/P67), nontransformed rat small intestinal IEC-6 relatively low only at high doses ERRP. Transforming factor-alpha heparin-binding factor-induced activation HER-2. growth- ligand-induced whereas effective HER-2-overexpressing trastuzumab, cetuximab, attenuated heregulin-alpha-induced expressed Furthermore, ERRP, significantly induced apoptosis None these agents either NIH-3T3 IEC Our results suggest an pan-erbB and, thus, be potential agent wide variety cancers subclasses EGFRs.