| PPAR
Is an APC-Regulated Target of Nonsteroidal Anti-Inflammatory
Drugs
Tong-Chuan He1, Timothy A. Chan1, Bert
Vogelstein2, and Kenneth W. Kinzler1
1 Johns Hopkins Oncology Center
and, Johns Hopkins University, Baltimore, Maryland 21231
2 The Howard Hughes Medical Institute, Johns Hopkins
University, Baltimore, Maryland 21231
Cell, Vol. 99, 335–345, October, 1999,
Copyright © 1999 by Cell Press
Download
to Citation Manager
Reprint
(PDF) Version of this Article - 451K
Search Medline for articles by:
Tong-Chuan
He || Kenneth
W. Kinzler
Abstract
PPAR
was identified as a target of APC through the analysis of
global gene expression profiles in human colorectal
cancer (CRC) cells. PPAR
expression was elevated in CRCs and repressed by
APC in CRC cells. This repression was mediated by
 -catenin/Tcf-4-responsive
elements in the PPAR
promotor. The ability of PPARs to bind eicosanoids
suggested that PPAR
might be a target of chemopreventive nonsteroidal anti-inflammatory
drugs (NSAIDs). Reporters containing PPAR-responsive
elements were repressed by the NSAID sulindac. Furthermore,
sulindac was able to disrupt the ability of PPAR
to bind its recognition sequences. These findings
suggest that NSAIDs inhibit tumorigenesis through inhibition
of PPAR,
the gene for which is normally regulated by APC.
Corresponding
author: Kenneth W. Kinzler, (410) 955 8886 (phone), (410)
955 0548 (fax), kinzlke@welchlink.welch.jhu.edu
|
