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dc.contributor.authorNagel, Jutta M.
dc.contributor.authorGeiger, Brenda Mae
dc.contributor.authorKaragiannis, Apostolos K. A.
dc.contributor.authorGras-Miralles, Beatriz
dc.contributor.authorHorst, David
dc.contributor.authorNajarian, Robert
dc.contributor.authorZiogas, Dimitrios C.
dc.contributor.authorChen, Xinhua
dc.contributor.authorKokkotou, Efi G.
dc.date.accessioned2013-03-25T17:25:45Z
dc.date.issued2012
dc.identifier.citationNagel, Jutta M., Brenda M. Geiger, Apostolos K. A. Karagiannis, Beatriz Gras-Miralles, David Horst, Robert M. Najarian, Dimitrios C. Ziogas, XinHua Chen, and Efi Kokkotou. 2012. Reduced intestinal tumorigenesis in APCmin mice lacking melanin-concentrating hormone. PLoS ONE 7(7): e41914.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10463176
dc.description.abstractBackground: Melanin-concentrating hormone (MCH) is an evolutionary conserved hypothalamic neuropeptide that in mammals primarily regulates appetite and energy balance. We have recently identified a novel role for MCH in intestinal inflammation by demonstrating attenuated experimental colitis in MCH deficient mice or wild type mice treated with an anti-MCH antibody. Therefore, targeting MCH has been proposed for the treatment of inflammatory bowel disease. Given the link between chronic intestinal inflammation and colorectal cancer, in the present study we sought to investigate whether blocking MCH might have effects on intestinal tumorigenesis that are independent of inflammation. Methodology Tumor development was evaluated in MCH-deficient mice crossed to the APCmin mice which develop spontaneously intestinal adenomas. A different cohort of MCH−/− and MCH+/+ mice in the APCmin background was treated with dextran sodium sulphate (DSS) to induce inflammation-dependent colorectal tumors. In Caco2 human colorectal adenocarcinoma cells, the role of MCH on cell survival, proliferation and apoptosis was investigated. Results: APCmin mice lacking MCH developed fewer, smaller and less dysplastic tumors in the intestine and colon which at the molecular level are characterized by attenuated activation of the wnt/beta-catenin signaling pathway and increased apoptotic indices. Form a mechanistic point of view, MCH increased the survival of colonic adenocarcinoma Caco2 cells via inhibiting apoptosis, consistent with the mouse studies. Conclusion: In addition to modulating inflammation, MCH was found to promote intestinal tumorigenesis at least in part by inhibiting epithelial cell apoptosis. Thereby, blocking MCH as a therapeutic approach is expected to decrease the risk for colorectal cancer.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0041914en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407051/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectEndocrine Systemen_US
dc.subjectEndocrine Physiologyen_US
dc.subjectBiochemistryen_US
dc.subjectNeurochemistryen_US
dc.subjectNeuroendocrinologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectSignal Transductionen_US
dc.subjectSignaling Cascadesen_US
dc.subjectWNT Signaling Cascadeen_US
dc.subjectNeuroscienceen_US
dc.subjectMedicineen_US
dc.subjectEndocrinologyen_US
dc.subjectGastroenterology and Hepatologyen_US
dc.subjectColonen_US
dc.subjectColon Anatomy and Developmenten_US
dc.subjectGastrointestinal Cancersen_US
dc.subjectInflammatory Bowel Diseaseen_US
dc.subjectOncologyen_US
dc.subjectBasic Cancer Researchen_US
dc.subjectTumor Physiologyen_US
dc.subjectCancers and Neoplasmsen_US
dc.subjectGastrointestinal Tumorsen_US
dc.subjectColon Adenocarcinomaen_US
dc.titleReduced Intestinal Tumorigenesis in APCmin Mice Lacking Melanin-Concentrating Hormoneen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKokkotou, Efi G.
dc.date.available2013-03-25T17:25:45Z
dc.identifier.doi10.1371/journal.pone.0041914*
dash.contributor.affiliatedGeiger, Brenda Mae
dash.contributor.affiliatedChen, Xinhua
dash.contributor.affiliatedNajarian, Robert M.
dash.contributor.affiliatedKokkotou, Efi


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