Prostaglandin E 2 regulates the complement inhibitor CD55/decay-accelerating factor in colorectal cancer

Vijaykumar R. Holla, Dingzhi Wang, Joanne R. Brown, Jason R. Mann, Sharada Katkuri, Raymond N. DuBois

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Cyclooxygenase-derived prostaglandin E 2 (PGE 2) stimulates tumor progression by modulating several proneoplastic pathways. The mechanisms by which PGE 2 promotes tumor growth and metastasis through stimulation of cell migration, invasion, and angiogenesis have been fairly well characterized. Much less is known, however, about the molecular mechanisms responsible for the immunosuppressive effects of PGE 2. We identified PGE 2 target genes and subsequently studied their biologic role in colorectal cancer cells. The complement regulatory protein decay-accelerating factor (DAF or CD55) was induced following PGE 2 treatment of LS174T colon cancer cells. Analysis of PGE 2-mediated activation of the DAF promoter employing 5′-deletion luciferase constructs suggests that regulation occurs at the transcriptional level via a cyclic AMP/ protein kinase A-dependent pathway. Nonsteroidal antiinflammatory drugs blocked DAF expression in HCA-7 colon cancer cells, which could be restored by the addition of exogenous PGE 2. Finally, we observed an increase in DAF expression in the intestinal mucosa of Apc Min+/- mice treated with PGE 2 in vivo. In summary, these results indicate a novel immunosuppressive role for PGE 2 in the development of colorectal carcinomas.

Original languageEnglish (US)
Pages (from-to)476-483
Number of pages8
JournalJournal of Biological Chemistry
Issue number1
StatePublished - Jan 7 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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