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

J Gastrointest Surg. May-Jun 2002;6(3):304-9. doi: 10.1016/s1091-255x(01)00041-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Isoenzymes
  • Tgfb1 protein, mouse
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Oncogene Protein p21(ras)