Journal Article

Coordinate regulation of cyclooxygenase-2 and TGF-β1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors

Jinyi Shao, Hongmiao Sheng, Radhika Aramandla, Michael A. Pereira, Ronald A. Lubet, Ernest Hawk, Liam Grogan, Ilan R. Kirsch, M. Kay Washington, R. Daniel Beauchamp and Raymond N. DuBois

in Carcinogenesis

Volume 20, issue 2, pages 185-191
Published in print February 1999 | ISSN: 0143-3334
Published online February 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.2.185
Coordinate regulation of cyclooxygenase-2 and TGF-β1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors

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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-β1 staining pattern in these human and rat tumors was similar to that observed for COX-2. The role of TGF-β in RER adenocarcinomas is complex because of the increased mutation rate of TGF-β type II receptors. Northern analysis showed abundant TGF-β1 mRNA in AOM-induced tumors, but not in paired mucosa. TGF-β1 induced the expression of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF-β1 treatment caused a TGF-β-dependent overexpression of COX-2 in rat intestinal epithelial cells (RIE-1). TGF-β1 may regulate COX-2 expression during the colonic adenoma to carcinoma sequence.

Keywords: AOM, azoxymethane; COX, cyclooxygenase; HNPCC, non-polyposis colorectal cancer; NSAID, non-steroidal anti-inflammatory drug; PBS, phosphate-buffered saline; RER, replication error-positive; TGF-β, transforming growth factor β.

Journal Article.  5438 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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