ENHANCED EXPRESSION OF A NEW CLASS OF LIVER-ENRICHED B-ZIP TRANSCRIPTION FACTORS, HEPATOCARCINOGENESIS-RELATED TRANSCRIPTION FACTOR, IN HEPATOCELLULAR CARCINOMAS OF RATS AND HUMANS

Rat hepatocarcinogenesis-related transcription factor (HTF) was earlie r identified as a b-Zip transcription factor in chemically induced rat hepatocellular carcinoma (HCC) by cDNA subtraction, and its structure was found to be different from that of the conventional b-Zip protein s. We investigated htf gene expression in rat tissues by Northern anal ysis and found that HTF expression was ubiquitous but was enriched in the liver. HTF expression increased concomitantly with HCC development in rat liver, and the HTF-containing DNA-binding factor also increase d. Stimulated HTF gene expression also was observed in rat regeneratin g livers, From the results of various assays, X-box-binding protein 1/ Tax-response element binding factor 5 was suggested to be a human homo logue of rat HTF. In humans, HTF gene expression was also abundant in the liver and was revealed to be specifically stimulated in HCCs, but not in other types of cancers, To our knowledge, HTF is the first exam ple of a liver-enriched transcription factor that exhibits HCC-associa ted gene expression. Injection of anti-HTF antibody decreased the grow th rate of cultured HCC cells. Consequently, HTF is thought to partici pate in hepatocyte growth as well as in hepatocarcinogenesis.