The majority of human pancreatic
adenocarcinomas display a ductal phenotype; experimental studies indicate that
tumors with this phenotype can arise from both acinar and ductal cells. In normal pancreas acinar cells, the pancreas
transcription factor 1 transcriptional complex is required for gene expression. Pancreas
transcription factor 1 is a heterooligomer of pancreas-specific (p48) and ubiquitous (p75/E2A and p64/HEB) basic helix-loop-helix
proteins. We have examined the role of p48 in the phenotype of
azaserine-induced rat DSL6
tumors and
cancers of the human exocrine pancreas. Serially transplanted acinar DSL6
tumors express p48 whereas DSL6-derived cell lines, and the
tumors induced by them, display a ductal phenotype and lack p48. In human
pancreas cancer cell lines and tissues, p48 is present in acinar
tumors but not in ductal
tumors. Transfection of ductal
pancreas cancers with p48
cDNA did not activate the expression of
amylase nor a reporter gene under the control of the rat
elastase promoter. In some cell lines, p48 was detected in the nucleus whereas in others it was cytoplasmic, as in one human acinar
tumor. Together with prior work, our findings indicate that p48 is associated with the acinar phenotype of exocrine pancreas
cancers and it is necessary, but not sufficient, for the expression of the acinar phenotype.