Jy. Shao et al., Coordinate regulation of cyclooxygenase-2 and TGF-beta 1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors, CARCINOGENE, 20(2), 1999, pp. 185-191
Evidence is accumulating which indicates that cyclo-oxygenase-2 (COX-2) is
involved in the pathogenesis of colorectal cancer. We evaluated the express
ion of COX-2 in replication error-positive (RER) colon cancers, colon cance
rs metastatic to liver and azoxymethane (AOM)induced rat colonic tumors. Im
munohistochemistry showed that COX-2 was low to undetectable in normal huma
n mucosa, but abundant in the RER adenocarcinomas we examined. COX-2 immuno
reactivity in metastatic colon cancers was less abundant, but clearly detec
table. In the colon of AOM-treated rats, COX-2 protein was not detectable i
n normal mucosa, but present in most of the epithelial cells comprising the
tumors. The TGF-beta 1 staining pattern in these human and rat tumors was
similar to that observed for COX-2, The role of TGF-beta in RER adenocarcin
omas is complex because of the increased mutation rate of TGF-beta type IT
receptors, Northern analysis showed abundant TGF-beta 1 mRNA in AOM-induced
tumors, but not in paired mucosa, TGF-beta 1 induced the expression of COX
-2 mRNA and protein in intestinal epithelial cells (IEC-6), Chronic TGF-bet
a 1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat in
testinal epithelial cells (RIE-1), TGF-beta 1 may regulate COX-2 expression
during the colonic adenoma to carcinoma sequence.