Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue.
Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
Ljubimova
J Y
JY
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Petrovic
L M
LM
Wilson
S E
SE
Geller
S A
SA
Demetriou
A A
AA
D018248:Adenoma, Liver Cell / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000418:Albumins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D000418:Albumins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases