Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development |
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| Authors: | Gironella Meritxell Seux Mylène Xie Min-Jue Cano Carla Tomasini Richard Gommeaux Julien Garcia Stephane Nowak Jonathan Yeung Man Lung Jeang Kuan-Teh Chaix Amandine Fazli Ladan Motoo Yoshiharu Wang Qing Rocchi Palma Russo Antonio Gleave Martin Dagorn Jean-Charles Iovanna Juan L Carrier Alice Pébusque Marie-Josèphe Dusetti Nelson J |
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| Affiliation: | Institut National de Santé et de Recherche Médicale, U624 Stress Cellulaire, F-13288 Marseille, France. |
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| Abstract: | Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1(-/-) mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/ras(V12) oncoproteins developed bigger tumors than TP53INP1(+/+) transformed MEFs or TP53INP1(-/-) transformed MEFs with restored TP53INP1 expression. Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity. |
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| Keywords: | apoptosis pancreatic cancer ponasterone A tumor suppressor micro RNA |
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