Hepatocyte growth factor induces pro-apoptotic genes in HepG2 hepatoma but not 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 process in this effect, we performed studies at cellular and molecular levels. HGF induced apoptosis only in HepG2 hepatoma cells at day 3 in about 20% of the 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 decisional 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 initial elevated growth rate and the absence of apoptosis involvement in the following cytostatic effect of HGF in melanoma cells. Consistent with this hypothesis, bax mRNA and protein levels were unchanged or even lower relative to control values.
Matteucci
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Institute of General Pathology, University of Milano, via L. Mangiagalli, 31-20133 Milano, Italy.
Castoldi
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Desiderio
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MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D004273:DNA, Neoplasm; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; C031017:ornithine decarboxylase antizyme; D017228:Hepatocyte Growth Factor; D009955:Ornithine Decarboxylase