Hepatocyte growth factor induces pro-apoptotic genes in HepG2 hepatoma butnot in B16-F1 melanoma cells

Hepatocyte growth factor (HGF) exerts a cytostatic effect on HepG2 and B16- F1 cell lines. To evaluate the possible involvement of the apoptotic proces s in this effect, we performed studies at cellular and molecular levels. HG F induced apoptosis only in HepG2 hepatoma cells at day 3 in about 20% of t he cells undergoing growth inhibition, while hallmarks of apoptosis did not occur in B16-F1 melanoma cells. During the first 24 h after HGF treatment, enhanced expression of the pro-apoptotic genes bax and c-Myc was observed at level of mRNA and protein. Concomitant induction of antizyme (AZ) might lower ornithine decarboxylase (ODC) protein level though a huge increase in ODC mRNA level took place. This was suggested as a signal for apoptosis de cisional phase. The levels of the proteins examined except that of AZ fell down thereafter when HepG2 cells underwent apoptosis. In B16-F1 cells, only ODC and AZ protein levels were elevated probably in relation to the initia l elevated growth rate and the absence of apoptosis involvement in the foll owing cytostatic effect of HGF in melanoma cells. Consistent with this hypo thesis, bax mRNA and protein levels were unchanged or even lower relative t o control values. (C) 2001 Wiley-Liss, Inc.