title: Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.
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.
authors.affiliation: Institut National de Santé et de Recherche Médicale, U624 Stress Cellulaire, F-13288 Marseille, France.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Mylène
authors.initials: M
authors.lastname: Seux
authors.forename: Min-Jue
authors.initials: MJ
authors.lastname: Xie
authors.forename: Carla
authors.initials: C
authors.lastname: Cano
authors.forename: Richard
authors.initials: R
authors.lastname: Tomasini
authors.forename: Julien
authors.initials: J
authors.lastname: Gommeaux
authors.forename: Stephane
authors.initials: S
authors.lastname: Garcia
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nowak
authors.forename: Man Lung
authors.initials: ML
authors.lastname: Yeung
authors.forename: Kuan-Teh
authors.initials: KT
authors.lastname: Jeang
authors.forename: Amandine
authors.initials: A
authors.lastname: Chaix
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Motoo
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Palma
authors.initials: P
authors.lastname: Rocchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Dagorn
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
authors.forename: Alice
authors.initials: A
authors.lastname: Carrier
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Pébusque
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Dusetti
mesh_terms: D000818:Animals; D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012334:RNA, Neoplasm / Q000235:genetics; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; C495901:TP53 protein, human; C429767:TP53INP1 protein, human; D016159:Tumor Suppressor Protein p53; C518507:tumor protein 53-induced nuclear protein 1, mouse