Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the expression of beta-catenin, leading to a rapid proliferation of pancreatic cells.
10.3858/emm.2011.43.2.010
- Author:
Il Rae CHO
1
;
Sang Seok KOH
;
Hye Jin MIN
;
Su Jin KIM
;
Yangsoon LEE
;
Eun Hee PARK
;
Srisuttee RATAKORN
;
Byung Hak JHUN
;
Sangtaek OH
;
Randal N JOHNSTON
;
Young Hwa CHUNG
Author Information
1. Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736, Korea. younghc@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
beta-catenin;
carcinoma, pancreatic ductal;
cyclic AMP-dependent protein kinases;
PAUF protein, human;
Wnt proteins
- MeSH:
*Adenocarcinoma/metabolism/pathology;
Cell Line, Tumor;
Cell Proliferation;
Cyclin D1/metabolism;
Gene Expression Regulation, Neoplastic;
Glycogen Synthase Kinase 3/metabolism;
HEK293 Cells;
Humans;
Lectins/genetics/*metabolism;
*Pancreatic Neoplasms/metabolism/pathology;
Phosphorylation;
Proto-Oncogene Proteins c-akt/metabolism;
Proto-Oncogene Proteins c-jun/metabolism;
Signal Transduction;
*Up-Regulation;
beta Catenin/genetics/*metabolism
- From:Experimental & Molecular Medicine
2011;43(2):82-90
- CountryRepublic of Korea
- Language:English
-
Abstract:
It is not yet understood how the enhanced expression of pancreatic adenocarcinoma up-regulated factor (PAUF; a novel oncogene identified in our recent studies), contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up-regulates the expression and transcriptional activity of beta-catenin while the suppression of PAUF by shRNA down-regulates beta-catenin. The induction of beta-catenin by PAUF is mediated by the activities of Akt and GSK-3beta, but inhibition of downstream ERK does not reduce beta-catenin expression. To test whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated signaling pathway for the stabilization of beta-catenin, we examined the phosphorylation status of beta-catenin in the presence of PAUF compared with that of beta-catenin during treatment with Wnt3a or dibutyryl cAMP, a cell permeable cyclic AMP analogue. PAUF expression induces phosphorylation at Ser-33/37/Thr-41 and Ser-675 of beta-catenin but no phosphorylation at Ser-45, indicating that a unique phosphorylation pattern of beta-catenin is caused by PAUF. Finally, the expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of beta-catenin, leading to a rapid proliferation of pancreatic cells; conversely decreased PAUF expression (by shRNA) results in the reduced proliferation of pancreatic cells. Treatment with hexachlorophene (an inhibitor of beta-catenin) reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken together, we propose that PAUF can up-regulate and stabilize beta-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells.
