Down-Regulation of SerumGlucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation 英文参考文献.docVIP

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Down-Regulation of SerumGlucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation 英文参考文献.doc

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Down-Regulation of SerumGlucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation 英文参考文献

Down-RegulationofSerum/GlucocorticoidRegulated Kinase1inColorectalTumoursIsLargelyIndependentof PromoterHypermethylation FrancescaLessi1,3,AndrewBeggs1,MariagraziadePalo2,MarcelloAnti2,RaffaeleMacaronePalmieri2, SimonaFrancesconi2,VitoGomes2,GenerosoBevilacqua3,IanTomlinson1,StefaniaSegditsas1* 1Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 2Presidio Ospedaliero BelcolleViterbo,Viterbo,Italy,3DivisionofSurgical,MolecularandUltrastructuralPathology,DepartmentofOncology,UniversityofPisaandPisaUniversityHospital,Pisa, Italy Abstract Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanismofgenesilencingincancer,wetestedwhethertheSGK1promoterregionwasmethylatedincolonictumour samples. Methodology/PrincipalFindings:WeinvestigatedthemethylationprofileofthetwoCpGislandspresentinthepromoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We furtherconfirmedourfindingsinapanelof10normaland10tumourcolonictissuesamplesofhumanorigin.Weobserved CpGmethylationonlyinthesmallerandmoredistalCpGislandinthepromoterregionofSGK1inbothnormalandtumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylationofthecorrespondingCpG. Conclusions/Significance:OurresultsshowthateventhoughpartialmethylationofthepromoterregionofSGK1ispresent, thisdoesnotaccountforthedifferentexpressionlevelsseenbetweennormalandtumourtissue. Citation: Lessi F, Beggs A, de Palo M, Anti M, Macarone Palmieri R, et al. (2010) Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal TumoursIsLargelyIndependentofPromoterHypermethylation.PLoSONE5(11):e13840.doi:10.1371/journal.pone.0013840 Editor:NicolettaLandsb