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Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the expression of beta-catenin, leading to a rapid proliferation of pancreatic cells
Experimental & Molecular Medicine ; : 82-90, 2011.
Artículo en Inglés | WPRIM | ID: wpr-186265
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.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Neoplasias Pancreáticas / Fosforilación / Adenocarcinoma / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Regulación hacia Arriba / Proteínas Proto-Oncogénicas c-jun / Ciclina D1 / Glucógeno Sintasa Quinasa 3 / Línea Celular Tumoral Tipo de estudio: Estudio pronóstico Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Neoplasias Pancreáticas / Fosforilación / Adenocarcinoma / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Regulación hacia Arriba / Proteínas Proto-Oncogénicas c-jun / Ciclina D1 / Glucógeno Sintasa Quinasa 3 / Línea Celular Tumoral Tipo de estudio: Estudio pronóstico Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2011 Tipo del documento: Artículo