Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12306
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dc.contributor.authorShin, Joongho-
dc.contributor.authorCarr, Azadeh-
dc.contributor.authorCorner, Georgia A-
dc.contributor.authorTögel, Lars-
dc.contributor.authorDávaos-Salas, Mercedes-
dc.contributor.authorTran, Hoanh-
dc.contributor.authorChueh, Anderly C-
dc.contributor.authorAl-Obaidi, Sheren-
dc.contributor.authorChionh, Fiona-
dc.contributor.authorAhmed, Naseem-
dc.contributor.authorBuchanan, Daniel D-
dc.contributor.authorYoung, Joanne P-
dc.contributor.authorMalo, Madhu S-
dc.contributor.authorHodin, Richard A-
dc.contributor.authorArango, Diego-
dc.contributor.authorSieber, Oliver M-
dc.contributor.authorAugenlicht, Leonard H-
dc.contributor.authorDhillon, Amardeep S-
dc.contributor.authorWeber, Thomas K-
dc.contributor.authorMariadason, John M-
dc.date.accessioned2015-05-16T01:58:12Z
dc.date.available2015-05-16T01:58:12Z
dc.date.issued2014-07-18-
dc.identifier.citationThe Journal of Biological Chemistry 2014; 289(36): 25306-16en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12306en
dc.description.abstractThe histone deacetylase inhibitor (HDACi) sodium butyrate promotes differentiation of colon cancer cells as evidenced by induced expression and enzyme activity of the differentiation marker intestinal alkaline phosphatase (ALPi). Screening of a panel of 33 colon cancer cell lines identified cell lines sensitive (42%) and resistant (58%) to butyrate induction of ALP activity. This differential sensitivity was similarly evident following treatment with the structurally distinct HDACi, MS-275. Resistant cell lines were significantly enriched for those harboring the CpG island methylator phenotype (p = 0.036, Chi square test), and resistant cell lines harbored methylation of the ALPi promoter, particularly of a CpG site within a critical KLF/Sp regulatory element required for butyrate induction of ALPi promoter activity. However, butyrate induction of an exogenous ALPi promoter-reporter paralleled up-regulation of endogenous ALPi expression across the cell lines, suggesting the presence or absence of a key transcriptional regulator is the major determinant of ALPi induction. Through microarray profiling of sensitive and resistant cell lines, we identified KLF5 to be both basally more highly expressed as well as preferentially induced by butyrate in sensitive cell lines. KLF5 overexpression induced ALPi promoter-reporter activity in resistant cell lines, KLF5 knockdown attenuated butyrate induction of ALPi expression in sensitive lines, and butyrate selectively enhanced KLF5 binding to the ALPi promoter in sensitive cells. These findings demonstrate that butyrate induction of the cell differentiation marker ALPi is mediated through KLF5 and identifies subsets of colon cancer cell lines responsive and refractory to this effect.en
dc.language.isoenen
dc.subject.otherCIMPen
dc.subject.otherColon Canceren
dc.subject.otherDNA Methylationen
dc.subject.otherDifferentiationen
dc.subject.otherHDACen
dc.subject.otherHistone Deacetylase Inhibitor (HDAC Inhibitor) (HDI)en
dc.subject.otherKruppel-like Factor (KLF)en
dc.subject.otherAlkaline Phosphatase.genetics.metabolismen
dc.subject.otherBenzamides.pharmacologyen
dc.subject.otherBinding Sites.geneticsen
dc.subject.otherBlotting, Westernen
dc.subject.otherButyric Acid.pharmacologyen
dc.subject.otherCell Differentiation.drug effects.geneticsen
dc.subject.otherCell Line, Tumoren
dc.subject.otherColonic Neoplasms.genetics.metabolism.pathologyen
dc.subject.otherCpG Islands.geneticsen
dc.subject.otherDrug Resistance, Neoplasm.geneticsen
dc.subject.otherEpithelial Cells.metabolismen
dc.subject.otherGene Expression Profilingen
dc.subject.otherHCT116 Cellsen
dc.subject.otherHT29 Cellsen
dc.subject.otherHistone Deacetylase Inhibitors.pharmacologyen
dc.subject.otherHumansen
dc.subject.otherKruppel-Like Transcription Factors.genetics.metabolismen
dc.subject.otherOligonucleotide Array Sequence Analysisen
dc.subject.otherPromoter Regions, Genetic.geneticsen
dc.subject.otherProtein Bindingen
dc.subject.otherPyridines.pharmacologyen
dc.subject.otherReverse Transcriptase Polymerase Chain Reactionen
dc.titleThe intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe Journal of biological chemistryen
dc.identifier.affiliationthe Walter and Eliza Hall Institute, Melbourne 3052, Australiaen
dc.identifier.affiliationthe Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australiaen
dc.identifier.affiliationthe Ludwig Institute for Cancer Research, Austin Health, Melbourne 3084, Australiaen
dc.identifier.affiliationthe Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115.en
dc.identifier.affiliationthe Group of Molecular Oncology, Centro en Investigación en Bioquímica y Biología Molecular-Nanomedicine, Vall d'Hebron University Hospital, Research Institute, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain and El Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Spain.en
dc.identifier.affiliationFrom the Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461.en
dc.identifier.affiliationPeter MacCallum Cancer Center, Melbourne 3002, Australia, and.en
dc.identifier.affiliationthe Veterans Affairs New York Harbor Health Care System, Brooklyn, New York 11209.en
dc.identifier.affiliationFrom the Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, the Ludwig Institute for Cancer Research, Austin Health, Melbourne 3084, Australia, john.mariadason@ludwig.edu.au.en
dc.identifier.doi10.1074/jbc.M114.557546en
dc.description.pages25306-16en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/25037223en
dc.type.contentTexten
dc.type.austinJournal Articleen
local.name.researcherMariadason, John M
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
Appears in Collections:Journal articles
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