A Conserved Tissue-Specific Homeodomain-Less Isoform of MEIS1 Is Downregulated in Colorectal Cancer 英文参考文献.docVIP

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A Conserved Tissue-Specific Homeodomain-Less Isoform of MEIS1 Is Downregulated in Colorectal Cancer 英文参考文献.doc

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A Conserved Tissue-Specific Homeodomain-Less Isoform of MEIS1 Is Downregulated in Colorectal Cancer 英文参考文献

AConservedTissue-SpecificHomeodomain-LessIsoform ofMEIS1IsDownregulatedinColorectalCancer RichardC.Crist1,JacquelynJ.Roth1,ScottA.Waldman2,ArthurM.Buchberg1* 1DepartmentofMicrobiologyandImmunology,ThomasJeffersonUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica,2DepartmentofPharmacologyand ExperimentalTherapeutics,ThomasJeffersonUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Colorectalcancerisoneofthemostcommoncancersindevelopednationsandistheresultofbothenvironmentaland genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encodehomeodomaintranscriptionfactors.TheMEIS1homeoboxgeneisknowntobeinvolvedinseveralhematological malignanciesandsolidtumorsandrecentevidencesuggeststhatexpressionoftheMEIS1transcriptisalteredincolorectal cancer.Despitethispotentialconnection,littleisknownabouttheroleofthegeneintheintestines.Weprobedmurine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing expression of two previously described isoforms,aswellastwonovelMeis1products.A32kDMeis1productwasexpressedinthenucleiofnon-epithelialcellsin thestomachandcolon,whilea27kDproductwasexpressedinthecytoplasmofepithelialcellsintheproximalcolon.Our datasuggestthatthe27kDand32kDMeis1proteinsarebothformsoftheMeis1dprotein,ahomeodomain-lessisoform whose transcript was previously identified in cDNA screens. Both the MEIS1D transcript and protein were expressed in humancolonmucosa.ExpressionoftheMEIS1Dproteinwasdownregulatedin83%(10/12)ofprimarycolorectalcancer samples compared to matched normal mucosa, indicating that MEIS1D is a biomarker of colorectal tumorigenesis. The decreasedexpressionofMEIS1Dincolontumorsalsosuggeststhatthisconservedhomeodomain-lessisoformmayactasa tumorsuppressorinhumancolorectalcancer. Citation:CristRC,RothJJ,WaldmanSA,BuchbergAM(2011)AConservedTissue-SpecificHomeodomain-LessIsoformofMEIS1IsDownregulatedinColorectal Cancer.PLoSONE6(8):e23665.doi:10.1371/jou