Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression

Jason R. Mann, Michael G. Backlund, F. Gregory Buchanan, Taki Daikoku, Vijaykumar R. Holla, Daniel W. Rosenberg, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Prostaglandin E2 (PGE2), a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis. PGE2 is a downstream product of cyclooxygenase (COX) and is biochemically inactivated by prostaglandin dehydrogenase (PGDH). In the present study, we investigated the mechanisms by which PGDH is down-regulated in cancer. We show that epidermal growth factor (EGF) represses PGDH expression in colorectal cancer cells. EGF receptor (EGFR) signaling induces Snail, which binds conserved E-box elements in the PGDH promoter to repress transcription. Induction of PGE2 catabolism through inhibition of EGFR signaling blocks cancer growth in vivo. In human colon cancers, elevated Snail expression correlates well with down-regulation of PGDH. These data indicate that PGDH may serve a tumor suppressor function in colorectal cancer and provide a possible COX-2-independent way to target PGE2 to inhibit cancer progression.

Original languageEnglish (US)
Pages (from-to)6649-6656
Number of pages8
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Mann, J. R., Backlund, M. G., Buchanan, F. G., Daikoku, T., Holla, V. R., Rosenberg, D. W., Dey, S. K., & DuBois, R. N. (2006). Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression. Cancer Research, 66(13), 6649-6656. https://doi.org/10.1158/0008-5472.CAN-06-1787