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, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    83 Scopus citations

    Abstract

    Evidence is accumulating which indicates that cycleoxygenase-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.

    Original languageEnglish (US)
    Pages (from-to)185-191
    Number of pages7
    JournalCarcinogenesis
    Volume20
    Issue number2
    DOIs
    StatePublished - 1999

    ASJC Scopus subject areas

    • Cancer Research

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