Obesity-Induced Increase in Tumor Necrosis Factor-alpha Leads to Development of Colon Cancer in Mice

dc.creatorFlores, MBS
dc.creatorRocha, GZ
dc.creatorDamas-Souza, DM
dc.creatorOsorio-Costa, F
dc.creatorDias, MM
dc.creatorRopelle, ER
dc.creatorCamargo, JA
dc.creatorde Carvalho, RB
dc.creatorCarvalho, HF
dc.creatorSaad, MJA
dc.creatorCarvalheira, JBC
dc.date2012
dc.dateSEP
dc.date2014-07-30T14:49:00Z
dc.date2015-11-26T16:46:16Z
dc.date2014-07-30T14:49:00Z
dc.date2015-11-26T16:46:16Z
dc.date.accessioned2018-03-28T23:32:04Z
dc.date.available2018-03-28T23:32:04Z
dc.identifierGastroenterology. W B Saunders Co-elsevier Inc, v. 143, n. 3, n. 741, n. +, 2012.
dc.identifier0016-5085
dc.identifierWOS:000308399300038
dc.identifier10.1053/j.gastro.2012.05.045
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/62288
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/62288
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1274463
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBACKGROUND & AIMS: Epidemiology studies have shown that obesity increases risk for colorectal cancer (CRC). We investigated the contribution of obesity-induced increases in levels of tumor necrosis factor (TNF)-alpha and hyperinsulinemia to the development of CRC in mice. METHODS: Lean and obese mice (C57BL6/J and ob/ob) were given a combination of azoxymethane and dextran sulfate sodium, which led to the development of CRC; lean and obese severe combined immunodeficient mice were injected with HT-29 cells. We analyzed the roles of TNF-alpha and insulin in the development of obesity-mediated CRC using immunoblot, immunohistochemical, and apoptosis assays. RESULTS: Genetic-and diet-induced obesity increased the incidence and size of tumors that developed after administration of azoxymethane and dextran sulfate sodium, compared with lean mice. HT-29 xenograft tumors grew more rapidly in obese than lean mice. Neutralization of TNF-alpha reduced activation of c-Jun N-terminal kinase, I kappa B kinase, and the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin signaling pathway; it also reduced the growth and development of tumors in obese mice. Reducing levels of insulin levels had no effect on tumor growth in obese mice. CONCLUSIONS: TNF-alpha contributes to colon tumor growth in obese mice. Reagents that inhibit TNF-alpha might prevent the development or progression of CRC in obese individuals.
dc.description143
dc.description3
dc.description741
dc.description+
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageen
dc.publisherW B Saunders Co-elsevier Inc
dc.publisherPhiladelphia
dc.publisherEUA
dc.relationGastroenterology
dc.relationGastroenterology
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectJNK
dc.subjectInflammation
dc.subjectInsulin Resistance
dc.subjectMouse Model
dc.subjectColitis-associated Carcinogenesis
dc.subjectInsulin-receptor Substrate-1
dc.subjectDextran Sulfate Sodium
dc.subjectNf-kappa-b
dc.subjectColorectal-cancer
dc.subjectTnf-alpha
dc.subjectSerine Phosphorylation
dc.subjectRheumatoid-arthritis
dc.subjectSignal-transduction
dc.subjectUlcerative-colitis
dc.titleObesity-Induced Increase in Tumor Necrosis Factor-alpha Leads to Development of Colon Cancer in Mice
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución