title: mRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas.
abstract: BACKGROUND
  There is a consistently reported relationship between the incidence of colon cancer and obesity. It is thought that adipose tissue, particularly visceral fat, which secretes systemic factors that alter immunological, metabolic and endocrine milieu and promotes insulin resistance by producing adipocytokines, is important in cancer progression. Systemic high concentrations of adipocytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and glucocorticoid metabolism-related genes have been associated with gastrointestinal cancer. However, limited information exists about the expression of these cytokines within tumour tissue.
  
  
  METHODS
  mRNA expression of TNF-α, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-α), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), plasminogen activator inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B and C colorectal adenocarcinomas using quantitative reverse transcription PCR and microarray technology. The mRNA expression level of analysed genes was compared between tumour tissue and normal mucosa from the same patients, and a correlation to mRNA expression of E-cadherin in the same tissue samples was also performed.
  
  
  RESULTS
  A highly significant difference in mRNA expression level of several of the analysed genes was observed between tumour tissue and the normal intestinal mucosa. Inverse correlation between mRNA expression of 11βHSD1, IL-6, GR-α and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was observed.
  
  
  CONCLUSIONS
  Results show that the adipocytokines and glucocorticoid metabolism-related genes are overexpressed in colorectal adenocarcinomas, and expression of these genes is associated with the downregulation of E-cadherin mRNA, connecting these genes to carcinogenesis and progression of colorectal cancer.
authors.affiliation: Surgical Department, Østfold Hospital Trust, 1600, Fredrikstad, Norway.
authors.forename: Ragnhild H
authors.initials: RH
authors.lastname: Størkson
authors.forename: Rolf
authors.initials: R
authors.lastname: Aamodt
authors.forename: Katja Kannisto
authors.initials: KK
authors.lastname: Vetvik
authors.forename: Kirsi
authors.initials: K
authors.lastname: Pietilainen
authors.forename: Geir
authors.initials: G
authors.lastname: Bukholm
authors.forename: Kristin
authors.initials: K
authors.lastname: Jonsdottir
authors.forename: Hilde S
authors.initials: HS
authors.lastname: Vollan
authors.forename: Tonje
authors.initials: T
authors.lastname: Sonerud
authors.forename: Torben
authors.initials: T
authors.lastname: Lüders
authors.forename: Morten B
authors.initials: MB
authors.lastname: Jacobsen
authors.forename: Ida R K
authors.initials: IR
authors.lastname: Bukholm
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D054392:Adipokines / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054392:Adipokines; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D005938:Glucocorticoids; D012333:RNA, Messenger