title: COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status.
abstract: BACKGROUND
  Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue.
  
  
  METHODS
  Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated.
  
  
  RESULTS
  Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue.
  
  
  CONCLUSIONS
  Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Annika Gustafsson
authors.initials: AG
authors.lastname: Asting
authors.forename: Helena
authors.initials: H
authors.lastname: Carén
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersson
authors.forename: Christina
authors.initials: C
authors.lastname: Lönnroth
authors.forename: Kristina
authors.initials: K
authors.lastname: Lagerstedt
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000503:physiopathology*; D019295:Computational Biology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000502:physiology*
chemical_list: D051546:Cyclooxygenase 2