Ljubimova J Y, Petrovic L M, Wilson S E, Geller S A, Demetriou A A
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
J Histochem Cytochem. 1997 Jan;45(1):79-87. doi: 10.1177/002215549704500111.
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.
肝细胞癌（HCC）是一种常见的癌症类型，每年约有26万新发病例，肝硬化通常被认为是HCC的主要诱发因素。然而，肝硬化和HCC中基因表达的具体变化仍不清楚。分析了肝细胞生长因子（HGF）、其受体c-met原癌基因、c-myc原癌基因和白蛋白的基因表达。通过聚合酶链反应（PCR）研究了7例正常人类肝脏、9例丙型肝炎肝硬化、12例酒精性肝硬化、2例肝腺瘤和12例HCC中的基因表达。通过免疫荧光染色揭示HGF和c-met蛋白。HGF mRNA在正常肝脏中未表达，但在腺瘤、80%的HCC以及一些肝硬化中被检测到。石蜡包埋和新鲜冷冻的组织样本得出了相似的结果。免疫组化数据与PCR结果相关，表明HGF/c-met系统在HCC中过表达。与正常肝脏相比，HCC中白蛋白基因表达降低，这与肿瘤肝细胞功能改变一致。HCC中HGF/c-met系统的表达升高可能在肿瘤发生和/或进展中起作用。HGF及其受体c-met蛋白的组织定位研究支持HGF在HCC中存在自分泌和旁分泌作用机制，而在正常肝脏中仅存在旁分泌作用机制。
