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PMID: 11226285 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 5 ·2001-02-27 ·Pages 2598-603

Park BH, Vogelstein B, Kinzler KW

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that have been implicated in a variety of biologic processes. The PPARdelta isotype was recently proposed as a downstream target of the adenomatous polyposis coli (APC)/beta-catenin pathway in colorectal carcinogenesis. To evaluate its role in tumorigenesis, a PPARdelta null cell line was created by targeted homologous recombination. When inoculated as xenografts in nude mice, PPARdelta -/- cells exhibited a decreased ability to form tumors compared with PPARdelta +/- and wild-type controls. These data suggest that suppression of PPARdelta expression contributes to the growth-inhibitory effects of the APC tumor suppressor.

MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal/pharmacology Apoptosis/drug effects Base Sequence Cell Transformation, Neoplastic/genetics Colorectal Neoplasms/genetics,pathology DNA Primers Humans Receptors, Cytoplasmic and Nuclear/genetics,physiology Sulindac/pharmacology Transcription Factors/genetics,physiology Tumor Cells, Cultured
Chemicals
Anti-Inflammatory Agents, Non-Steroidal DNA Primers Receptors, Cytoplasmic and Nuclear Transcription Factors Sulindac
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Park B H
Johns Hopkins Oncology Center and Howard Hughes Medical Institute, 1650 Orleans Street, Room 590, Baltimore, MD 21231, USA.
Vogelstein B
Kinzler K W
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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.051630998
Published
2001-02-27
Pages
2598-603
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC30184
Subset
IM
Grants
NCI NIH HHS · CA57345 · United States
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · CA62924 · United States
NCI NIH HHS · R37 CA057345 · United States
NCI NIH HHS · R01 CA057345 · United States
External Links
PubMed source DOI: 10.1073/pnas.051630998 PMC Full Text View journal details
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