COEXPRESSION OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR AND RELATED PEPTIDES IN HUMAN GASTRIC-CARCINOMA

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-E GF) is a member of the EGF family of polypeptide growth factors, which includes EGF, transforming growth factor alpha (TGF-alpha), amphiregu lin (AR) and betacellulin (ETC). To assess the potential role of HB-EG F in human gastric carcinomas, the expression of HB-EGF and EGF recept or (EGF-R) was examined in normal and cancerous gastric tissues and cu ltured gastric cancer cell lines. By Northern blot analysis, there was a 4.7-fold increase in HB-EGF mRNA levels in human gastric cancers co mpared with normal gastric tissues. There was a concomitant 3.9-fold i ncrease in EGF-R mRNA levels in these cancers. Immunostaining revealed co-localization in 72% of the cancer cells of HB-EGF and EGF-R. AR an d ETC moieties were not evident by Northern blot analysis. However, us ing PCR, both AR and ETC mRNA species were demonstrated in normal and cancerous gastric tissues. By Northern blot analysis, HB-EGF, TGF-alph a, AR, ETC and EGF-R mRNA moieties were co-expressed in KATO III and N CI-N87 gastric cancer cell lines. Furthermore, HB-EGF, EGF and TGF-alp ha enhanced the growth of both cell lines in a dose-dependent manner. Our findings suggest that HB-EGF is relatively abundant in human gastr ic cancers and that coexpression of the EGF ligand family may lead to excessive activation of EGF-R in this disorder. (C) 1996 Wiley-Liss, I nc.