PROHIBITIN EXPRESSION IS DECREASED IN THE REGENERATING LIVER BUT NOT IN CHEMICALLY-INDUCED HEPATIC-TUMORS IN RATS

Expression of prohibitin, a growth-regulatory protein, was immunohisto chemically investigated in normal rat tissues, regenerating livers, an d chemically induced preneoplastic and neoplastic hepatic lesions. Spe cific cell types including hepatocytes, striated and smooth muscle cel ls, cardiac cells, squamous epithelial cells, sebaceous gland cells, h air root outer sheath cells, salivary gland duct epithelial cells, cho ndrocytes, immature spermatocytes and oocytes were found to be positiv e. In regenerating livers, prohibitin protein disappeared as early as 3 h after two-thirds hepatectomy and returned to near the original lev el by 24 h, while its mRNA level did not markedly vary. The timing of the disappearance was coincident with the expression of c-myc, suggest ing a relation to quiescent hepatocytes entering the cell cycle. Howev er, no pronounced decrease was evident in the most hyperplastic hepati c nodules and hepatocellular carcinomas investigated. Examination of 9 rat hepatocellular carcinoma cell lines, 6 hyperplastic hepatic nodul es and 5 hepatocellular carcinomas revealed a single case of a base su bstitution in prohibitin cDNA, identified as a synonymous sense change . The observed abundant expression of prohibitin in quiescent hepatocy tes and its rapid loss under conditions of regeneration indicate a gro wth-regulatory function, but our results do not suggest any critical r ole in rat hepatocarcinogenesis.