Nuclear
phosphoprotein 32 (pp32) inhibits K-ras induced transformation in experimental models. pp32
mRNA expression correlates with differentiation status in breast and
prostate cancers. In this study, we evaluated pp32
protein expression in relation to the differentiation status of pancreatic ductal
adenocarcinomas and precursor lesions of the
pancreatic cancers. pp32 expression showed strong nuclear staining in normal pancreatic acini and ducts. The intensity of this staining was maintained in pancreatic intraepithelial
neoplasia, intraductal papillary
mucinous neoplasms with mild dysplasia, well-differentiated
adenocarcinomas, and in a subset of moderately differentiated
adenocarcinomas. pp32 staining was absent or reduced in poorly differentiated
tumors and in intraductal papillary
mucinous neoplasms with moderate dysplasia. We validated pp32 expression by a second technique, immunoblot analysis of lysates from resected pancreatic ductal
adenocarcinomas and
pancreatic cancer cell lines. The well-differentiated
pancreatic cancer cell line HPAC expressed high amounts of pp32, as compared to the poorly differentiated
pancreatic cancer cell lines MiaPaCa2, Pl19, and Pl21 cells. Artificial introduction of pp32 expression into a poorly differentiated cell line, MiaPaCa2, caused an increase in G1 arrest compared to control cells. On the basis of this study and previous functional work that shows pp32 can inhibit K-ras transformation, we propose that reduction in pp32 expression levels may be a critical event in the progression of pancreatic
tumorigenesis in an aggressive subset of pancreatic ductal
adenocarcinomas.