1. Colitis and Colitis-Associated Cancer Are Exacerbated in Mice Deficient for Tumor Protein 53-Induced Nuclear Protein 1▿
- Author
-
Sylvia Pietri, Bernard Malissen, Carla E. Cano, Juan L. Iovanna, Stéphane Garcia, Meritxell Gironella, Julien Gommeaux, Marcel Culcasi, Marie-Josèphe Pébusque, Alice Carrier, Nelson Dusetti, Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie, biologie et radicaux libres - UMR 6517 (CBRL), Université de la Méditerranée - Aix-Marseille 2-Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
- Subjects
Colorectal cancer ,MESH: NF-kappa B ,medicine.disease_cause ,Inflammatory bowel disease ,MESH: Mice, Knockout ,MESH: Lipid Peroxidation ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,MESH: Colitis ,MESH: Animals ,Nuclear protein ,Mice, Knockout ,0303 health sciences ,MESH: Oxidative Stress ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Dextran Sulfate ,NF-kappa B ,MESH: Reactive Oxygen Species ,Nuclear Proteins ,Articles ,Colitis ,3. Good health ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Acute Disease ,Colonic Neoplasms ,MESH: Acute Disease ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Mutation ,MESH: Carrier Proteins ,Biology ,03 medical and health sciences ,medicine ,Animals ,Molecular Biology ,MESH: Mice ,Acute colitis ,Carcinogen ,030304 developmental biology ,MESH: Colonic Neoplasms ,MESH: Dextran Sulfate ,Azoxymethane ,MESH: Chronic Disease ,Cell Biology ,medicine.disease ,Oxidative Stress ,chemistry ,MESH: Cell Transformation, Neoplastic ,Immunology ,Chronic Disease ,Mutation ,Cancer research ,Lipid Peroxidation ,Carcinogenesis ,Carrier Proteins ,Reactive Oxygen Species ,MESH: Nuclear Proteins - 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.
- Published
- 2007
- Full Text
- View/download PDF