The Tissue-Specific Gene Expression during Progression of Mouse Hepatocellular Carcinoma

Expression of hepato-specific genes in slow- and fast-growing hepatocellular murine carcinomas was studied. A fast-growing dedifferentiated transplantable hepatocarcinoma variant (fgHCC) arose from the highly differentiated slow-growing hepatocarcinoma (sgHCC). In contrast to the parental hepatocarcinoma, expression of the hepatocyte nuclear factor 4 (HNF4), one of the key regulators of hepatocyte differentiation, and several HNF-4-responsive genes, transferrin, transthyretin, hepatocyte nuclear factor 1 (HNF1), and serum albumin, was downregulated in fgHCC. The expression of exogenous HNF4 in the fgHCC cell culture partially restored the expression of hepato-specific genes and led to the formation of epithelial islets in the culture. The described system may serve as an appropriate model for further analysis of mechanisms underlying hepatocarcinogenesis and liver tumor progression.