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

Saman Arbabi, Matthew R. Rosengart, Iris Garcia, Sandra Jelacic, Ronald V. Maier

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish
Pages (from-to)60-64
Number of pages5
JournalJournal of Surgical Research
Issue number1
StatePublished - May 2001


  • Carcinoma
  • Colon
  • Cyclooxygenase (COX)
  • Epithelium
  • Lipopolysaccharide
  • Mitogen-activated protein kinase (MAPK)
  • Neoplasm
  • Osmolarity
  • Rectum
  • Signal transduction


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