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PMID: 15665104 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Wnt/beta-catenin signaling pathway targets PPARgamma activity in colon cancer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 5 ·2005-02-01 ·Pages 1460-5

Jansson EA, Are A, Greicius G, Kuo IC, Kelly D, Arulampalam V, Pettersson S

Abstract

Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/beta-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APCMin) mouse cancer model, PPARgamma expression in the colonic mucosa is markedly altered. In addition, PPARgamma protein levels are elevated, possibly through sequestration by activated beta-catenin in colon cancer cell lines. Induction of the Wnt/beta-catenin pathway by LiCl also elevated PPARgamma levels and induced PPARgamma-dependent reporter and endogenous target genes. Mechanistically, PPARgamma, through interactions with beta-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.

MeSH Terms
Adenomatous Polyposis Coli/genetics Animals Base Sequence Cadherins/physiology Cell Line Cell Line, Tumor Cell Nucleus/physiology Colonic Neoplasms Cytoskeletal Proteins/physiology DNA Primers Genes, APC Genes, Reporter Humans Intercellular Signaling Peptides and Proteins/physiology Intestinal Mucosa/physiology Kidney Mice PPAR gamma/genetics,physiology RNA, Messenger/genetics Rats Recombinant Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction Trans-Activators/physiology Transfection Wnt Proteins beta Catenin
Chemicals
CTNNB1 protein, human CTNNB1 protein, mouse Cadherins Ctnnb1 protein, rat Cytoskeletal Proteins DNA Primers Intercellular Signaling Peptides and Proteins PPAR gamma RNA, Messenger Recombinant Proteins Trans-Activators Wnt Proteins beta Catenin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Jansson Emmelie A
Microbiology and Tumor Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden.
Are Alexandra
Greicius Gediminas
Kuo I-Chun
Kelly Denise
Arulampalam Velmurugesan
Pettersson Sven
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0405928102
Published
2005-02-01
Epub
2005-00-21
Pages
1460-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC547827
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0405928102 PMC Full Text View journal details
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