15-lipoxygenase-2 gene regulation by its product 15-(S)-hydroxyeicosatetraenoic acid through a negative feedback mechanism that involves peroxisome proliferator-activated receptor γ

被引:22
作者
Subbarayan, V.
Krieg, P.
Hsi, L. C.
Kim, J.
Yang, P.
Sabichi, A. L.
Llansa, N.
Mendoza, G.
Logothetis, C. J.
Newman, R. A.
Lippman, S. M.
Menter, D. G.
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Unit 1360, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA
[4] German Canc Res Ctr, Dept Eicosanoids & Tumor Dev, D-6900 Heidelberg, Germany
关键词
15-lipoxygenase-2; prostate cancer; gene expression; peroxisome proliferator-activated receptor gamma;
D O I
10.1038/sj.onc.1209617
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An inverse relationship exists between the expression of 15-lipoxygenase-2 (15-LOX-2) and peroxisome proliferator-activated receptor c (PPARc) in normal prostate epithelial cells (PrECs) compared with their expression in prostate carcinoma cells (PC-3). The reason for this difference, however, is unknown. We hypothesized that this inverse expression partly involves the 15-LOX-2 promoter and 15-S-hydroxyeicosatetraenoic acid (15-(S)HETE), a product of 15- LOX-2 that binds to PPARc. We identified an active steroid nuclear receptor half-site present in the 15-LOX-2 promoter fragment F-5 (-618/+177) that can interact with PPARc. After forced expression of wild-type PPARc, 15-(S)-HETE (1 mu M) decreased F-5 reporter activity in PrECs whereas forced expression of 15-LOX-2 resulted in 15-(S)-HETE production which enhanced F-5 activity in PC-3. In contrast, the expression of dominant-negative PPARc reversed the transcriptional activation of F-5 by enhancing it 202-fold in PrEC or suppressing it in PC-3; the effect in PC-3 was positively increased 150-fold in the presence of 15-(S)-HETE (1 mu M). Peroxisome proliferator-activated receptor c interacted with 15-LOX-2 promoter sequences in pulldown experiments using biotinylated 15-LOX-2 (-560/-596 bp) oligonucleotides. In gelshift analyses PPARc and orphan receptor ROR alpha were shown to interact with the F-5 fragment in PC-3 cells. These data suggest that crosstalk mechanisms exist between the 15-LOX-2 gene and PPARc to counterbalance expression and help explain the inverse relationship of these genes in normal versus cancer cells.
引用
收藏
页码:6015 / 6025
页数:11
相关论文
共 40 条
[1]   Identification of a novel DNA regulatory element in the rabbit surfactant protein B (SP-B) promoter that is a target for ATF/CREB and AP-1 transcription factors [J].
Berhane, K ;
Boggaram, V .
GENE, 2001, 268 (1-2) :141-151
[2]   Cell-autonomous induction of functional tumor suppressor 15-lipoxygenase 2 (15-LOX2) contributes to replicative senescence of human prostate progenitor cells [J].
Bhatia, B ;
Tang, SH ;
Yang, PY ;
Doll, A ;
Aumüeller, G ;
Newman, RA ;
Tang, DG .
ONCOGENE, 2005, 24 (22) :3583-3595
[3]   Subcellular localization and tumor-suppressive functions of 15-lipoxygenase 2 (15-LOX2) and its splice variants [J].
Bhatia, B ;
Maldonado, CJ ;
Tang, SH ;
Chandra, D ;
Klein, RD ;
Chopra, D ;
Shappell, SB ;
Yang, PY ;
Newman, RA ;
Tang, DG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :25091-25100
[4]   Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation [J].
Blanquart, C ;
Barbier, O ;
Fruchart, JC ;
Staels, B ;
Glineur, C .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2003, 85 (2-5) :267-273
[5]   Discovery of a second 15S-lipoxygenase in humans [J].
Brash, AR ;
Boeglin, WE ;
Chang, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (12) :6148-6152
[6]  
Butler R, 2000, CELL GROWTH DIFFER, V11, P49
[7]  
Cato A.C., 2002, SCI STKE, V2002, pre9, DOI [DOI 10.1126/STKE.2002.138.RE9, 10.1126/stke.2002.138.re9]
[8]   Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2 [J].
Elbrecht, A ;
Chen, YL ;
Cullinan, CA ;
Hayes, N ;
Leibowitz, MD ;
Moller, DE ;
Berger, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 224 (02) :431-437
[9]   Enzyme association with PPARγ:: evidence of a new role for 15-lipoxygenase type 2 [J].
Flores, AM ;
Li, L ;
McHugh, NG ;
Aneskievich, BJ .
CHEMICO-BIOLOGICAL INTERACTIONS, 2005, 151 (02) :121-132
[10]   ISOFORM-SPECIFIC AMINO-TERMINAL DOMAINS DICTATE DNA-BINDING PROPERTIES OF ROR-ALPHA, A NOVEL FAMILY OF ORPHAN HORMONE NUCLEAR RECEPTORS [J].
GIGUERE, V ;
TINI, M ;
FLOCK, G ;
ONG, E ;
EVANS, RM ;
OTULAKOWSKI, G .
GENES & DEVELOPMENT, 1994, 8 (05) :538-553