Elevated cyclooxygenase-2 levels in Min mouse adenomas.
OBJECTIVE
Mutations in the APC gene result in an increased propensity to develop intestinal neoplasia; however, a complete understanding of the mechanisms resulting in tumor formation has remained elusive. Min mice possess a mutation in the APC gene and display a neoplastic phenotype similar to that observed in familial adenomatous polyposis coli in humans. Cyclooxygenase (COX) inhibitors decrease tumor multiplicity in the Min mouse intestine. The present study was designed to determine if there was an increase in COX-2 in adenomas harvested from Min mouse intestine.


METHODS
COX-2 messenger RNA levels were determined by Northern blots and reverse-transcription polymerase chain reactions of B6Min x 129 mouse-derived tumors. Protein levels and localization were determined by Western blots and immunohistochemical staining.


RESULTS
The Northern blots revealed an approximately threefold increase in the level of COX-2 messenger RNA in Min mouse adenoma compared with normal mucosa. COX-2 protein levels in adenomatous tissues were also approximately threefold higher compared with normal mucosa from the same mouse. Immunohistochemical staining with a monospecific COX-2 antibody confirmed that increases in COX-2 immunoreactivity were restricted to dysplastic and neoplastic foci within intestinal mucosa.


CONCLUSIONS
These data show that COX-2 levels may be increased at an early stage in colorectal neoplasia during polyp formation and before invasion.
Williams
C S
CS
Department of Medicine, Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Luongo
C
C
Radhika
A
A
Zhang
T
T
Lamps
L W
LW
Nanney
L B
LB
Beauchamp
R D
RD
DuBois
R N
RN
D000236:Adenoma / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D017491:Genes, APC; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000235:genetics; D007527:Isoenzymes / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000235:genetics
D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases