Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells.
Recently we demonstrated in a transgenic mouse model that hepatocyte growth factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory effects of HGF in carcinogenesis were further characterized using a series of rat liver epithelial (RLE) cell lines which were transformed in vitro with either aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and enhanced cell motility in spontaneously and aflatoxin-transformed cells. In normal RLE cells HGF was slightly stimulatory and did not induce scattering. The HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is functionally active and capable of signaling events. In the aflatoxin transformed cells HGF also induced apoptosis, associated with constitutive c-myc expression and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell lines may provide a useful model to further examine the mechanism(s) by which HGF and its receptor modulate neoplastic development.
Conner
E A
EA
Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Wirth
P J
PJ
Kiss
A
A
Santoni-Rugiu
E
E
Thorgeirsson
S S
SS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004847:Epithelial Cells; D015870:Gene Expression; D016259:Genes, myc; D016158:Genes, p53; D006131:Growth Inhibitors / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000166:cytology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D019859:Proto-Oncogene Proteins c-met; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D006131:Growth Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019000:Phosphotyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases