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Induction of cyclooxygenase-2 and invasiveness by transforming growth factor-beta(1) in immortalized mouse colonocytes expressing oncogenic Ras.

Roman CD, Morrow J, Whitehead R, Beauchamp RD
J Gastrointest Surg. 2002 6 (3): 304-9

PMID: 12022979 · DOI:10.1016/s1091-255x(01)00041-5

Cyclooxygenase-2 (COX-2) expression appears to be important in colorectal carcinogenesis. Elevated COX-2 expression and activity have been observed in several different transformed cell types. Prior studies implicating involvement of the Ras oncogene and growth factors on COX-2 expression were largely derived from rat small intestinal cell lines. We have investigated whether mouse colonocyte COX-2 levels are regulated by oncogenic Ras or transforming growth factor-beta(1) (TGF-beta(1)), and whether these factors also serve to regulate cellular invasiveness. Young adult mouse colonocyte cells are colonocytes derived from the "Immortomouse" and immortalized by the SV40 large T antigen. Young adult mouse colonocyte Ras cells were derived by transfection of young adult mouse colonocyte cells with oncogenic Ha-Ras and are known to be tumorigenic. We found that the induction of COX-2 and eicosanoid release were augmented in the presence of activated Ras and that TGF-beta(1) caused a further increase in COX-2 in the Ras-transformed mouse colonocytes. Increased COX-2 expression was correlated with increased release of prostaglandins E(2) and I(2). Activated Ras and TGF-beta increased the invasiveness of the young adult mouse colonocyte cells, but treatment with a COX-2 inhibitor did not inhibit invasiveness. Thus we found that transforming growth factor-beta collaborates to increase COX-2 expression, protaglandin release, and invasiveness in mouse colonocytes, but the increased COX-2 activity does not appear to contribute to the invasive response.

MeSH Terms (12)

Animals Cells, Cultured Colon Colorectal Neoplasms Cyclooxygenase 2 Gene Expression Regulation, Neoplastic Isoenzymes Mice Oncogene Protein p21(ras) Prostaglandin-Endoperoxide Synthases Transforming Growth Factor beta Transforming Growth Factor beta1

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