title: Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1.
abstract: Tumor protein 53-induced nuclear protein 1 (TP53INP1) is an antiproliferative and proapoptotic protein involved in cell stress response. To address its physiological roles in colorectal cancer and colitis, we generated and tested the susceptibility of Trp53inp1-deficient mice to the development of colorectal tumors induced by injection of the carcinogen azoxymethane followed by dextran sulfate sodium (DSS)-induced chronic colitis. Trp53inp1-deficient mice showed an increased incidence and multiplicity of tumors compared to those of wild-type (WT) mice. Furthermore, acute colitis induced by DSS treatment was more severe in Trp53inp1-deficient mice than in WT mice. Treatment with the antioxidant N-acetylcysteine prevented colitis and colitis-associated tumorigenesis more efficiently in WT mice than in Trp53inp1-deficient mice, suggesting a higher oxidative load in the latter. Consistently, we demonstrated by electron spin resonance and spin trapping that colons derived from deficient mice produced more free radicals than those of the WT during colitis and that the basal blood level of the antioxidant ascorbate was decreased in Trp53inp1-deficient mice. Collectively, these results indicate that the oxidative load is higher in Trp53inp1-deficient mice than in WT mice, generating a more-severe DSS-induced colitis, which favors development of colorectal tumors in Trp53inp1-deficient mice. Therefore, TP53INP1 is a potential target for the prevention of colorectal cancer in patients with inflammatory bowel disease.
authors.affiliation: INSERM, U624 Stress cellulaire, 13288 Marseille Cedex 9, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Gommeaux
authors.forename: Carla
authors.initials: C
authors.lastname: Cano
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Sylvia
authors.initials: S
authors.lastname: Pietri
authors.forename: Marcel
authors.initials: M
authors.lastname: Culcasi
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Pébusque
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Nelson
authors.initials: N
authors.lastname: Dusetti
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.forename: Alice
authors.initials: A
authors.lastname: Carrier
mesh_terms: D000208:Acute Disease; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003110:Colonic Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016264:Dextran Sulfate / Q000494:pharmacology; D015227:Lipid Peroxidation; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; C518507:tumor protein 53-induced nuclear protein 1, mouse; D016264:Dextran Sulfate