Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester.

DuBois RN, Awad J, Morrow J, Roberts LJ, Bishop PR
J Clin Invest. 1994 93 (2): 493-8

PMID: 8113389 · PMCID: PMC293869 · DOI:10.1172/JCI116998

Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.

MeSH Terms (24)

Animals Cell Division Cell Line DNA DNA Probes Eicosanoids Electron Transport Complex IV Enzyme Induction Epithelial Cells Epithelium Gene Expression Regulation, Enzymologic Indomethacin Intestinal Mucosa Kinetics Mice Microsomes Prostaglandin-Endoperoxide Synthases Rats RNA, Messenger Sulindac Tetradecanoylphorbol Acetate Thymidine Transfection Transforming Growth Factor alpha

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