Prostaglandin E 2 enhances intestinal adenoma growth via activation of the ras-mitogen-activated protein kinase cascade

Dingzhi Wang, F. Gregory Buchanan, Haibin Wang, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

A large body of clinical, genetic, and biochemical evidence indicates that cyclooxygenase-2 (COX-2), a key enzyme for prostanoid biosynthesis, contributes to the promotion of colorectal cancer. COX-2-derived prostaglandin E 2 (PGE 2) is the most abundant prostaglandin found in several gastrointestinal malignancies. Although PGE 2 enhances intestinal adenoma growth in Apc min mice, the mechanism(s) by which it accelerates tumor growth is not completely understood. Here we investigated how PGE 2 promotes intestinal tumor growth and the signaling pathways responsible for its effects. We observed that PGE 2 treatment leads to increased epithelial cell proliferation and induces COX-2 expression in intestinal adenomas. Furthermore, we show that PGE 2 regulation of COX-2 expression is mediated by activation of a Ras-mitogen-activated protein kinase signaling cascade. One intriguing finding is that COX-2-derived PGE 2 mimics the effects of constitutively active Ras through a self amplifying loop that allows for a distinct growth advantage.

Original languageEnglish (US)
Pages (from-to)1822-1829
Number of pages8
JournalCancer Research
Volume65
Issue number5
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

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Prostaglandins E
Mitogen-Activated Protein Kinases
Adenoma
Cyclooxygenase 2
Growth
Prostaglandins
Neoplasms
Molecular Biology
Colorectal Neoplasms
Epithelial Cells
Cell Proliferation
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prostaglandin E 2 enhances intestinal adenoma growth via activation of the ras-mitogen-activated protein kinase cascade. / Wang, Dingzhi; Buchanan, F. Gregory; Wang, Haibin; Dey, Sudhansu K.; DuBois, Raymond N.

In: Cancer Research, Vol. 65, No. 5, 01.03.2005, p. 1822-1829.

Research output: Contribution to journalArticle

Wang, Dingzhi ; Buchanan, F. Gregory ; Wang, Haibin ; Dey, Sudhansu K. ; DuBois, Raymond N. / Prostaglandin E 2 enhances intestinal adenoma growth via activation of the ras-mitogen-activated protein kinase cascade. In: Cancer Research. 2005 ; Vol. 65, No. 5. pp. 1822-1829.
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