Correlation of hepatocyte growth factor-induced proliferation and calcium-activated potassium current in human gastric cancer cells

Hepatocyte growth factor (HGF) has been found to stimulate proliferation and migration of human gastric carcinoma cells. Whether the HGF-induced responses are correlated with the expressed level of HGF receptors or the changes of ionic currents is not clear. The present study investigated the effects of HGF on the proliferation and ionic currents of two human gastric adenocarcinoma cell lines, which were found to express different amounts of HGF receptor. Results showed that HGF induced a dose-dependent growth stimulation and accelerated cell cycle progression in SC-M1 cells. In patch clamp study, HGF treatment induced an outward K⁺ current and increased the slope conductance at -80 mV from 110 ± 15 pS/pF to 207 ± 15 pS/pF. The HGF-induced K⁺ current was abolished when tetraethylammonium chloride was added in bathing solution or a low Ca²⁺ solution was included in the recording pipette. Furthermore, HGF (10 ng/ml) induced an oscillatory Ca²⁺-activated K⁺ current with a lag period of 5 ± 3 min in SC-M1 cells. In contrast, HGF did not induce mitogenesis, cell cycle progression and changes in ionic currents in KATO-III cells, although this cell line expressed a higher level of HGF receptors than SC-M1 cells did. These findings provide evidence that the activity of Ca²⁺-activated KC channel may be involved in the HGF-induced cell proliferation in human gastric cancer cells, but it did not correlate with the density of HGF receptors.