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dc.contributor.authorFirestein, Ron
dc.contributor.authorBlander, Gil
dc.contributor.authorMichan, Shaday
dc.contributor.authorOberdoerffer, Philipp
dc.contributor.authorLuikenhuis, Sandra
dc.contributor.authorde Cabo, Rafael
dc.contributor.authorGuarente, Leonard P.
dc.contributor.authorOgino, Shuji
dc.contributor.authorCampbell, Jennifer
dc.contributor.authorBhimavarapu, Anupama
dc.contributor.authorFuchs, Charles Stewart
dc.contributor.authorHahn, William C.
dc.contributor.authorSinclair, David Andrew
dc.date.accessioned2010-12-09T15:35:45Z
dc.date.issued2008
dc.identifier.citationFirestein, Ron, Gil Blander, Shaday Michan, Philipp Oberdoerffer, Shuji Ogino, Jennifer Campbell, Anupama Bhimavarapu, et al. 2008. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 3(4): e2020.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4621701
dc.description.abstractNumerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a β-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates β-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of β-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of β−catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in β−catenin-driven malignancies.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0002020en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289879/pdf/en_US
dash.licenseLAA
dc.subjectcell growth and divisionen_US
dc.subjectcell signalingen_US
dc.subjectcellular death and stress responsesen_US
dc.subjectgene expressionen_US
dc.subjectgastrointestinal cancersen_US
dc.subjectpathophysiologyen_US
dc.subjecttranscription initiation and activationen_US
dc.titleThe SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growthen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorOgino, Shuji
dc.date.available2010-12-09T15:35:45Z
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dc.identifier.doi10.1371/journal.pone.0002020*
dash.authorsorderedfalse
dash.contributor.affiliatedBhimavarapu, Anupama
dash.contributor.affiliatedCampbell, Jennifer
dash.contributor.affiliatedSinclair, David
dash.contributor.affiliatedHahn, William
dash.contributor.affiliatedFuchs, Charles
dash.contributor.affiliatedOgino, Shuji


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