Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.

Details

Serval ID
serval:BIB_E4C9D3899591
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.
Journal
Cancer Cell
Author(s)
Wang D., Wang H., Shi Q., Katkuri S., Walhi W., Desvergne B., Das S.K., Dey S.K., DuBois R.N.
ISSN
1535-6108[print], 1535-6108[linking]
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
6
Number
3
Pages
285-295
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.
Keywords
1-Phosphatidylinositol 3-Kinase/metabolism, Adenoma/metabolism, Animals, Cell Survival, Chromones/pharmacology, Colorectal Neoplasms/metabolism, Dinoprostone/metabolism, Dinoprostone/pharmacology, Genes, APC, Humans, Male, Mice, Morpholines/pharmacology, Protein-Serine-Threonine Kinases/metabolism, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-akt, Receptors, Cytoplasmic and Nuclear/metabolism, Transcription Factors/metabolism, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:27
Last modification date
20/08/2019 16:08
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