Exp Mol Med.
2011 Feb;43(2):82-90. 10.3858/emm.2011.43.2.010.
Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the expression of beta-catenin, leading to a rapid proliferation of pancreatic cells
- Affiliations
-
- 1Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736, Korea. younghc@pusan.ac.kr
- 2Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
- 3Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea.
- 4Department of Nanomedical Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736, Korea.
- 5Pharmaco Genomics Research Center, Inje University, Busan 614-735, Korea.
- 6Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
- KMID: 1097265
- DOI: http://doi.org/10.3858/emm.2011.43.2.010
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.
Keyword
MeSH Terms
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*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
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