Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer.

Autor: Arbabi S; Department of Surgery, University of Washington School of Medicine, Seattle, Washington 98104, USA. sarbabi@u.washington.edu, Rosengart MR, Garcia I, Jelacic S, Maier RV
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2001 May 01; Vol. 97 (1), pp. 60-4.
DOI: 10.1006/jsre.2001.6112
Abstrakt: Background: Recent studies indicate a close relationship between cyclooxygense-2 (COX-2) expression and the pathogenesis of colorectal cancer, yet little information exists regarding the stimuli and pathways involved in COX-2 expression by the colonic epithelium. We studied the induction of COX-2 in response to such environmental stress as hyperosmolarity and lipopolysaccharide (LPS) in a human colon cell line. We further investigated the transduction cascades mediating COX-2 expression, focusing upon the mitogen-activated protein kinase pathways p38 and extracellular signal-regulated kinase (ERK).
Materials and Methods: Human colon cancer cells (Caco-2) were stimulated with increasing concentrations of sodium chloride (NaCl) or LPS. Total protein was extracted at different time points and subjected to Western blot analysis with antibodies to human COX-2, COX-1, or phospho-specific antibodies to ERK and p38.
Results: LPS failed to induce COX-2 or COX-1 expression. Hyperosmolarity induced COX-2 expression by 2 h, with peak levels occurring at 6-8 h. NaCl at 40 and 100 mM induced a 2-fold and more than 50-fold increase in COX-2 expression, respectively; COX-1 expression was not affected. Hyperosmolarity induced both p38 and ERK activation within 30 min; however, only p38 inhibition attenuated osmotic-induced COX-2 expression; inhibition of ERK activation had no effect.
Conclusions: Increase in osmolarity activates p38 and induces COX-2 expression in the colonic epithelium. The lack of response to LPS is teleologically expected of the colonic epithelium that is in constant contact with the fecal bacteria. This model also predicts that an increase in luminal osmolarity in the colon may induce COX-2 and thereby promote a neoplastic phenotype.
(Copyright 2001 Academic Press.)
Databáze: MEDLINE
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