Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.

Antonio Russo, Carla Cano, Qing Wang, Amandine Chaix, Martin Gleave, Alice Carrier, Yoshiharu Motoo, Ladan Fazli, Meritxell Gironella, Richard Tomasini, Nelson J. Dusetti, Kuan-Teh Jeang, Jean-Charles Dagorn, Palma Rocchi, Marie-Josèphe Pébusque, Juan L. Iovanna, Stephane Garcia, Min-Jue Xie, Julien Gommeaux, Lung Yeung ManMylène Seux, Jonathan Nowak

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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.
Lingua originaleEnglish
pagine (da-a)16170-16175
Numero di pagine6
RivistaProceedings of the National Academy of Sciences of the United States of America
Volume104
Stato di pubblicazionePublished - 2007

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    Russo, A., Cano, C., Wang, Q., Chaix, A., Gleave, M., Carrier, A., Motoo, Y., Fazli, L., Gironella, M., Tomasini, R., Dusetti, N. J., Jeang, K-T., Dagorn, J-C., Rocchi, P., Pébusque, M-J., Iovanna, J. L., Garcia, S., Xie, M-J., Gommeaux, J., ... Nowak, J. (2007). Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proceedings of the National Academy of Sciences of the United States of America, 104, 16170-16175.