EXPRESSION RATIO OF HEPATOCYTE NUCLEAR FACTOR-I TO VARIANT HEPATOCYTENUCLEAR FACTOR-I IN DIFFERENTIATION OF HEPATOCELLULAR-CARCINOMA AND HEPATOBLASTOMA

Background/Aims: Liver-specific protein genes have multiple cis-/trans -acting elements, but those accountable for hepatocytic differentiatio n are unclear. An AT-rich core sequence (AT moth) is essential as a ci s-acting element for the hepatic transcription. Homologous proteins he patocyte nuclear factor-1 (HNF-1) and variant HNF-1 (vHNF-1) bind to t his moth The ratio of HNF-1 to vHNF-1 mRNA was examined in various liv er tissues with respect to their differentiation. Methods: The competi tive reverse transcriptional polymerase chain reaction was employed to amplify HNF-1 and vHNF-1 mRNA simultaneously and to examine their exp ression ratio in total RNA extracted from frozen liver tissues of 37 p atients with hepatocellular carcinoma, five patients with hepatoblasto ma, and 15 non-neoplastic liver tissues. Results: The ratio of HNF-1 t o vHNF-1 mRNA was higher in well-differentiated cases than in poorly-d ifferentiated and undifferentiated cases, except that one poorly-diffe rentiated hepatoblastoma displayed a high ratio. Non-neoplastic liver tissues had low ratios similar to poorly-differentiated hepatocellular carcinoma, the reason for which remained unknown. However, chronic he patitis and liver cirrhosis cases also demonstrated low ratios, and he nce degenerative changes themselves displayed no obvious influence on such ratios. Thus, the gene expression of HNF-1 and vHNF-1 seemed to b e differentially regulated in neoplastic and nonneoplastic hepatocytes . Conclusions: These results suggested that the ratio of HNF-1 to vHNF -1 mRNA correlated with histological differentiation of HCC and hepato blastoma.