title: Expression of COX-2 and Wnt pathway genes in adenomas of familial adenomatous polyposis patients treated with meloxicam.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited predisposition to colorectal cancer caused by germline mutations within the adenomatous polyposis coli (APC) gene, a key member of the Wnt signalling pathway. A new class of non-steroidal anti-inflammatory drugs (NSAIDs), the specific cyclooxygenase 2 (COX-2) inhibitors, have recently been applied for the treatment of FAP patients.
  
  
  METHODS
  The expressions of the Wnt members and targets APC, c-myc, cyclin D1 and COX-2, as measured by real-time quantitative RT-PCR, have been evaluated in fresh samples of normal colorectal mucosa and matched adenoma tissue of six unrelated FAP patients before and after treatment with meloxicam.
  
  
  RESULTS
  A significant up-regulation of COX-2 in adenomas after treatment with meloxicam was found. Furthermore, in adenomas, a down-regulation of APC after treatment and a tight correlation of the expressions of the two Wnt targets, c-myc and cyclin D1, in both stages of treatment were observed.
  
  
  CONCLUSIONS
  A feedback loop mediated by the peroxisome proliferator-activated receptor (PPAR) gamma is discussed as being responsible for the up-regulation of COX-2
authors.affiliation: Division of Medical Genetics, University Clinics, Basel, Switzerland.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Dobbie
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Muller
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Christiane
authors.initials: C
authors.lastname: Albrecht
authors.forename: Daniel
authors.initials: D
authors.lastname: D'Orazio
authors.forename: Igor
authors.initials: I
authors.lastname: Bendik
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Bauerfeind
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000188:drug therapy / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019938:Cyclin D1 / Q000235:genetics; D051546:Cyclooxygenase 2; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017491:Genes, APC / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D051153:Wnt Proteins; D029961:Zebrafish Proteins
chemical_list: D000970:Antineoplastic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D013843:Thiazines; D013844:Thiazoles; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D000077239:Meloxicam