Overexpression of cyclooxygenase 2 in hamartomatous polyps of Peutz-Jeghers syndrome.
OBJECTIVE
Peutz-Jeghers syndrome (PJS) is an autosomal-dominant hamartomatous polyposis syndrome. Affected individuals are at risk for intestinal and extraintestinal malignancies. Prostaglandins and polyamines are small molecules believed to be important in tumor formation and growth. Cyclooxygenase (COX) and ornithine decarboxylase (ODC) are key enzymes in the prostaglandin and polyamine biosynthetic pathways, respectively. The aim of this study was to measure and compare COX-1 and COX-2 expression in normal and hamartomatous tissue of PJS patients.


METHODS
We measured COX-1 and COX-2 protein expression in normal and hamartomatous GI tissues from affected PJS individuals and compared it with that in normal controls. COX-2 RNA in these tissues was also measured and compared by reverse transcription polymerase chain reaction (PCR). In addition, COX-2 expression was detected in tissue slides by immunostaining. ODC activity was measured between normal and hamartomatous tissues of PJS compared with control tissues.


RESULTS
COX-1 expression was similar in normal and control GI tissues. In contrast, COX-2 overexpression was noted in hamartomatous polyp tissue from PJS patients compared with normal control and PJS tissue. COX-2 expression by reverse transcription PCR was 10-fold greater in a hamartoma compared with other tissues. COX-2 expression was noted in the epithelial cells of hamartomatous polyps, and also coursing throughout the stromal tissue of the lamina propria, including muscle cells. ODC activity was similar in the tissues studied.


CONCLUSIONS
Selective COX-2 overexpression was noted in hamartomatous polyp tissue from PJS individuals. The results of the study provide an avenue for possible effective chemoprevention of polyp formation and growth in PJS.
McGarrity
Thomas J
TJ
Department of Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033-0850, USA.
Peiffer
Laurie P
LP
Amos
Christopher I
CI
Frazier
Marsha L
ML
Ward
Margaret G
MG
Howett
Mary K
MK
D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D066246:ErbB Receptors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006222:Hamartoma / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007417:Intestinal Polyps / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics; D008565:Membrane Proteins; D010580:Peutz-Jeghers Syndrome / Q000201:enzymology* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors