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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1238-1244 |
| Number of pages | 7 |
| Journal | Modern Pathology |
| Volume | 20 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 14 2007 |
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Keywords
- Intraductal papillary mucinous neoplasms
- Pancreatic ductal adenocarcinoma
- Poorly differentiated pancreatic adenocarcinomas
- pp32 (ANP32A)
- Protein expression
- Tumor suppressor
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia. / Brody, Jonathan R.; Witkiewicz, Agnes; Williams, Timothy K.; Kadkol, Shrihari S.; Cozzitorto, Joseph; Durkan, Brandice; Pasternack, Gary R.; Yeo, Charles J.
In: Modern Pathology, Vol. 20, No. 12, 14.12.2007, p. 1238-1244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia
AU - Brody, Jonathan R.
AU - Witkiewicz, Agnes
AU - Williams, Timothy K.
AU - Kadkol, Shrihari S.
AU - Cozzitorto, Joseph
AU - Durkan, Brandice
AU - Pasternack, Gary R.
AU - Yeo, Charles J.
PY - 2007/12/14
Y1 - 2007/12/14
N2 - 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.
AB - 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.
KW - Intraductal papillary mucinous neoplasms
KW - Pancreatic ductal adenocarcinoma
KW - Poorly differentiated pancreatic adenocarcinomas
KW - pp32 (ANP32A)
KW - Protein expression
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=36249024805&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36249024805&partnerID=8YFLogxK
U2 - 10.1038/modpathol.3800974
DO - 10.1038/modpathol.3800974
M3 - Article
C2 - 17906614
AN - SCOPUS:36249024805
VL - 20
SP - 1238
EP - 1244
JO - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
SN - 0893-3952
IS - 12
ER -