Expression of HNF-1 alpha and HNF-1 beta in various histological differentiations of hepatocellular carcinoma.

Hepatic nuclear factor 1 (HNF-1) regulates genes in a hepatocyte-specific manner. It has been previously reported that the ratio of HNF-1 alpha and HNF-1 beta mRNA is related to histological differentiation hepatocellular carcinoma (HCC). In this study, the expression levels of the HNF-1 alpha and HNF-1 beta proteins were analysed relatively and quantitatively in various histologically differentiated HCC and surrounding non-cancerous tissues, and HNF-1 alpha binding activity for the AT element of the B domain of the human alpha-fetoprotein enhancer was examined. Western blot analysis demonstrated that HNF-1 alpha protein was expressed at a higher level in well-differentiated HCC tissues than in the surrounding non-HCC tissues; on the other hand, the HNF-1 alpha protein was expressed at lower levels in moderately and poorly differentiated HCCs than in the surrounding non-HCC tissues. The levels of HNF-1 beta expression in well-differentiated and poorly differentiated HCCs were similar to and higher than those found in the respective surrounding non-cancerous portions. In binding assays, HNF-1 binding activity was high in well-differentiated HCC and lower in moderately and poorly differentiated HCCs. Most well-differentiated HCC cases showed immunohistochemical expression of HNF-1 alpha. These findings show that poor histological differentiation of HCC correlates with decreases in the level and activity of HNF-1 alpha proteins.