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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 82 - 90 (9page)
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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 β-catenin while the suppression of PAUF by shRNA down-regulates β-catenin. The induction of β-catenin by PAUF is mediated by the activities of Akt and GSK-3β, but inhibition of downstream ERK does not reduce β-catenin expression.
To test whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated signaling pathway for the stabilization of β-catenin, we examined the phosphorylation status of β-catenin in the presence of PAUF compared with that of β-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 β-catenin but no phosphorylation at Ser-45,indicating that a unique phosphorylation pattern of β-catenin is caused by PAUF. Finally, the expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of β-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 β-catenin) reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken together, we propose that PAUF can up-regulate and stabilize β-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells.
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참고문헌 (26)
참고문헌 신청
/ 200707 / EGF receptor is involved in WNT3a-mediated proliferation and motility of NIH3T3 cells via ERK pathway activation / CELLULAR SIGNALLING 19 : 1554 ~ 1564
Aberle H / 1997 / Beta-catenin is a target for the ubiquitin-proteasome pathway / EMBO J 16 : 3797 ~ 3804
Ayroldi E / 2002 / Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1 / Mol Cell Biol 22 : 7929 ~ 7941
Castellone MD / 2009 / The beta-catenin axis integrates multiple signals downstream from RET/ papillary thyroid carcinoma leading to cell proliferation / Cancer Res 69 : 1867
Choi SH / 2008 / Novel cationic solid lipid nanoparticles enhanced p53 gene transfer to lung cancer cells / Eur J Pharm Biopharm 68 : 545 ~ 554
Aberle H / 1997 / Beta-catenin is a target for the ubiquitin-proteasome pathway / EMBO J 16 : 3797 ~ 3804
Ayroldi E / 2002 / Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1 / Mol Cell Biol 22 : 7929 ~ 7941
Castellone MD / 2009 / The beta-catenin axis integrates multiple signals downstream from RET/ papillary thyroid carcinoma leading to cell proliferation / Cancer Res 69 : 1867
Choi SH / 2008 / Novel cationic solid lipid nanoparticles enhanced p53 gene transfer to lung cancer cells / Eur J Pharm Biopharm 68 : 545 ~ 554
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