Robert Beauchamp
Principal Investigator
Last active: 10/31/2018

Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors.

Shao J, Sheng H, Aramandla R, Pereira MA, Lubet RA, Hawk E, Grogan L, Kirsch IR, Washington MK, Beauchamp RD, DuBois RN
Carcinogenesis. 1999 20 (2): 185-91

PMID: 10069452 · DOI:10.1093/carcin/20.2.185

Evidence is accumulating which indicates that cyclooxygenase-2 (COX-2) is involved in the pathogenesis of colorectal cancer. We evaluated the expression of COX-2 in replication error-positive (RER) colon cancers, colon cancers metastatic to liver and azoxymethane (AOM)-induced rat colonic tumors. Immunohistochemistry showed that COX-2 was low to undetectable in normal human mucosa, but abundant in the RER adenocarcinomas we examined. COX-2 immunoreactivity in metastatic colon cancers was less abundant, but clearly detectable. In the colon of AOM-treated rats, COX-2 protein was not detectable in normal mucosa, but present in most of the epithelial cells comprising the tumors. The TGF-beta1 staining pattern in these human and rat tumors was similar to that observed for COX-2. The role of TGF-beta in RER adenocarcinomas is complex because of the increased mutation rate of TGF-beta type II receptors. Northern analysis showed abundant TGF-beta1 mRNA in AOM-induced tumors, but not in paired mucosa. TGF-beta1 induced the expression of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF-beta1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat intestinal epithelial cells (RIE-1). TGF-beta1 may regulate COX-2 expression during the colonic adenoma to carcinoma sequence.

MeSH Terms (22)

Animals Azoxymethane Carcinogens Colon Colonic Neoplasms Cyclooxygenase 1 Cyclooxygenase 2 Enzyme Induction Epithelial Cells Humans Immunohistochemistry Intestinal Mucosa Isoenzymes Liver Neoplasms Male Membrane Proteins Neoplasm Proteins Prostaglandin-Endoperoxide Synthases Rats Rats, Inbred F344 RNA, Messenger Transforming Growth Factor beta

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