6533b86cfe1ef96bd12c824d
RESEARCH PRODUCT
Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.
Meritxell GironellaRichard TomasiniJulien GommeauxYoshiharu MotooMartin E. GleaveMin-jue XieMarie-josèphe PébusqueAntonio RussoMan Lung YeungCarla E. CanoMylène SeuxStéphane GarciaLadan FazliPalma RocchiJuan L. IovannaKuan-teh JeangAmandine ChaixNelson DusettiJonathan A. NowakJean-charles DagornAlice CarrierQing Wangsubject
Settore MED/06 - Oncologia MedicaTransplantation HeterologousGene ExpressionMice NudeMicePancreatic tumorPancreatic cancerCell Line TumormicroRNAGene expressionmedicineAnimalsHumansRNA NeoplasmNuclear proteinCaspaseHeat-Shock ProteinsMice KnockoutMultidisciplinarybiologyBase Sequenceapoptosis pancreatic cancer ponasterone A tumor suppressor micro RNANuclear ProteinsBiological Sciencesmedicine.diseaseTransplantationPancreatic NeoplasmsMicroRNAsCell Transformation NeoplasticApoptosisCancer researchbiology.proteinTumor Suppressor Protein p53Carrier ProteinsNeoplasm TransplantationCarcinoma Pancreatic Ductaldescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-10-09 | Proceedings of the National Academy of Sciences of the United States of America |