Epidermal growth factor and 17beta-estradiol effects on proliferation of a human gastric cancer cell line (AGS)

BACKGROUND: Recent evidence suggests that both estrogens and growth factors play an important role in the growth of gastrointestinal tumors. The expression of estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the gastrointestinal tract might therefore result in functional cross-talk between estrogens and EGF. The aim of the present study was to evaluate in vitro the effects of 17beta-estradiol and EGF administration on cell proliferation of a human gastric adenocarcinoma cell line (AGS) and investigate whether any interaction of these compounds may play a role in regulating gastric cancer cell proliferation. METHODS: Estrogen and EGFRs were detected by enzyme immunoassay. Cell proliferation was assessed with the MTT test. RESULTS: Exposure of AGS cells to increasing concentrations of 17beta-estradiol showed an anti-proliferative action at concentrations of 2 microM or higher. The addition of increasing concentrations of EGF stimulated cell growth, with a maximal response at 50 ng/ml EGF. The effect of increasing 17beta-estradiol concentrations combined with 50 ng/ml EGF was to increase cell growth at the lower estradiol concentrations. At the highest estradiol concentration the EGF proliferative effect was suppressed, and a decrease in proliferation rates occurred. Moreover, a significant negative correlation was found between 17beta-estradiol concentrations and EGFR expression. CONCLUSIONS: These findings suggest that growth of cultured gastric cancer cells (AGS) might be modulated by sex steroid hormones through interaction with EGF.