The tissue-specific gene expression during progression of mouse hepatocellular carcinoma

Expression of hepato-specific genes in slow- and fast-growing hepatocellula r murine carcinomas was studied. A fast-growing dedifferentiated transplant able hepatocarcinoma variant (fgHCC) arose from the highly differentiated s low-growing hepatocarcinoma (sgHCC). In contrast to the parental hepatocarc inoma, expression of the hepatocyte nuclear factor 4 (HNF4), one of the key regulators of hepatocyte differentiation, and several HNF-4-responsive gen es, transferrin, transthyretin, hepatocyte nuclear factor 1 (HNF1), and ser um albumin, was downregulated in fgHCC. The expression of exogenous HNF4 in the fgHCC cell culture partially restored the expression of hepato-specifi c genes and led to the formation of epithelial islets in the culture. The d escribed system may serve as an appropriate model for further analysis of m echanisms underlying hepatocarcinogenesis and liver tumor progression.