Expression of Epidermal Growth Factor, Transforming Growth Factor‐α and Their Receptor Genes in Human Gastric Carcinomas; Implication for Autocrine Growth

ABSTRACT

The expressions of mRNA for epidermal growth factor (EGF), transforming growth factor‐α (TGF‐α) and EGF receptor (EGFR) genes were examined in 7 human gastric carcinoma cell lines and 15 gastric carcinoma tissues and the corresponding normal mucosas. All of the gastric carcinoma cell lines expressed mRNA for EGFR and TGF‐α genes. TMK‐1 and MKN‐28 cells also expressed EGF mRNA. Production of EGF, TGF‐α and EGFR protein by gastric carcinoma cell lines was also confirmed by EGF and TGF‐α specific monoclonal antibody binding. As for surgical specimens, EGFR and TGF‐α mRNA were detected at high levels in all the tumor tissues. Interestingly, EGF mRNA was detected in 5 (33.3%) of the 15 gastric carcinomas but it was not detected in normal tissues. Moreover, anti‐EGF and anti‐TGF‐α monoclonal antibodies inhibited the spontaneous ³H‐TdR uptake by gastric carcinoma cells. These results suggest that EGF and/or TGF‐α produced by tumor cells act as autocrine growth factors for gastric carcinomas.