Role of the basic helix-loop-helix transcription factor p48 in the differentiation phenotype of exocrine pancreas cancer cells

The majority of human pancreatic adenocarcinomas display a ductal phenotype ; experimental studies indicate that tumors with this phenotype can arise f rom both acinar and ductal cells. In normal pancreas acinar cells, the panc reas transcription factor 1 transcriptional complex is required for gene ex pression. Pancreas transcription factor 1 is a heterooligomer of pancreas-s pecific (p48) and ubiquitous (p75/E2A and p64/HEB) basic helix-loop-helix p roteins. We have examined the role of p48 in the phenotype of azaserine-ind uced rat DSL6 tumors and cancers of the human exocrine pancreas. Serially t ransplanted acinar DSL6 tumors express p48 whereas DSL6-derived cell lines, and the tumors induced by them, display a ductal phenotype and lack p48, I n human pancreas cancer cell lines and tissues, p48 is present in acinar tu mors but not in ductal tumors. Transfection of ductal pancreas cancers with p48 cDNA did not activate the expression of amylase nor a reporter gene un der the control of the rat elastase promoter. In some cell lines, p48 was d etected in the nucleus whereas in others it was cytoplasmic, as in one huma n acinar tumor. Together with prior work, our findings indicate that p48 is associated with the acinar phenotype of exocrine pancreas cancers and it i s necessary, but not sufficient, for the expression of the acinar phenotype .