title: Down-regulation of serum/glucocorticoid regulated kinase 1 in colorectal tumours is largely independent of promoter hypermethylation.
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 mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples.
  
  
  RESULTS
  We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG.
  
  
  CONCLUSIONS
  Our results show that even though partial methylation of the promoter region of SGK1 is present, this does not account for the different expression levels seen between normal and tumour tissue.
authors.affiliation: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lessi
authors.forename: Andrew
authors.initials: A
authors.lastname: Beggs
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: de Palo
authors.forename: Marcello
authors.initials: M
authors.lastname: Anti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Macarone Palmieri
authors.forename: Simona
authors.initials: S
authors.lastname: Francesconi
authors.forename: Vito
authors.initials: V
authors.lastname: Gomes
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Stefania
authors.initials: S
authors.lastname: Segditsas
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001374:Azacitidine; D000077209:Decitabine; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011965:Receptors, Glucocorticoid; D000099184:Serum-Glucocorticoid Regulated Kinases