Induction of cyclooxygenase-2 and invasiveness by transforming growth factor-β1 in immortalized mouse colonocytes expressing oncogenic ras View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-06

AUTHORS

Christopher D. Roman, Jason Morrow, Robert Whitehead, R. Daniel Beauchamp

ABSTRACT

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. More... »

PAGES

304-309

Identifiers

URI

http://scigraph.springernature.com/pub.10.1016/s1091-255x(01)00041-5

DOI

http://dx.doi.org/10.1016/s1091-255x(01)00041-5

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12022979


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