Co-expression of heparin-binding EGF-like growth factor and related peptides in human gastric carcinoma

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family of polypeptide growth factors, which includes EGF, transforming growth factor α (TGF-α), amphiregulin (AR) and betacellulin (BTC). To assess the potential role of HB EGF in human gastric carcinomas, the expression of HB-EGF and EGF receptor (EGF-R) was examined in normal and cancerous gastric tissues and cultured gastric cancer cell lines. By Northern blot analysis, there was a 4.7-fold increase in HB-EGF mRNA levels in human gastric cancers compared with normal gastric tissues. There was a concomitant 3.9-fold increase in EGF-R mRNA levels in these cancers. Immunostaining revealed co-localization in 72% of the cancer cells of HB-EG and EGF-R. AR and ETC moieties were not evident by Northern blot analysis. However, using FOR, both AR and ETC mRNA species were demonstrated in normal and cancerous gastric tissues. By Northern blot analysis, HB-EGF, TGF-α, AR, BC and EGF-R mRNA moieties were co expressed in KATO Ill ad NCI-N87 gastric cancer cell lines. Furthermore, HB-EGF, EGF and TGF-α enhanced the growth of both cell lines in a dose-dependent manner. Our findings suggest that HB-EGF is relatively abundant in human gastric cancers and that coexpression of the EGF ligand family may lead to excessive activation of EGF-R in this disorder.