Expression of COX-2 and Wnt pathway genes in adenomas of familial adenomatous polyposis patients treated with meloxicam.
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
Dobbie
Zuzana
Z
Division of Medical Genetics, University Clinics, Basel, Switzerland.
Muller
Patrick Y
PY
Heinimann
Karl
K
Albrecht
Christiane
C
D'Orazio
Daniel
D
Bendik
Igor
I
Müller
Hansjakob
H
Bauerfeind
Peter
P
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
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