Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia.

Authors

• Jonathan R Brody
• Agnes Witkiewicz
• Timothy K Williams
• Shrihari S Kadkol
• Joseph Cozzitorto
• Brandice Durkan
• Gary R Pasternack
• Charles J Yeo

Publication/Presentation Date

12-1-2007

Abstract

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.

Volume

20

Issue

12

First Page

1238

Last Page

1244

ISSN

0893-3952

Published In/Presented At

Brody, J. R., Witkiewicz, A., Williams, T. K., Kadkol, S. S., Cozzitorto, J., Durkan, B., Pasternack, G. R., & Yeo, C. J. (2007). Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 20(12), 1238–1244. https://doi.org/10.1038/modpathol.3800974

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

17906614

Department(s)

Administration and Leadership

Document Type

Article