Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin

Recent investigations indicate that telomerase activity regulates the life span of cells by compensating for telomere shortening during DNA replicatio n. In addition, as differentiation progresses, telomerase activity is reduc ed in several different cell lineages. These endings lend support to the th eory that more immature cells have greater remaining proliferative capacity and longer life span. However, it has not been directly demonstrated that the differentiation along a hepatocytic or a bile ductal lineage is accompa nied by reduction of telomerase activity. In this study, we present direct evidence that telomerase activity is reduced during hepatocytic and biliary epithelial differentiation by using our unique cell lines including a stem -like cell line, ETK-1. When hepatocytic differentiation was induced in ETK -1 by 5-azacytidine, telomerase activity decreased significantly. Similarly , when we compared the telomerase activity on SSP-25 and RBE cell lines fro m the same origin but representing different maturation stages of cholangio carcinoma, more mature cells were found to possess significantly lower acti vity. These results indicate that the generally accepted relationship betwe en telomerase activity and differentiation stage also applies in the hepato cytic and biliary epithelial lineages. Copyright (C) 2001 John Wiley & Sons , Ltd.