PMID- 11212240
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 2
DP  - 2001 Jan 15
TI  - 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated 
      receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells.
PG  - 497-503
AB  - 15-Lipoxygenase (15-LOX)-2 is expressed in benign prostate secretory cells and 
      benign prostate produces 15S-hydroxyeicosatetraenoic acid (15S-HETE) from 
      exogenous arachidonic acid (AA). In contrast, 15S-LOX-2 and 15S-HETE formation 
      are reduced in prostate carcinoma (Pca). The mechanisms whereby reduced 15-LOX-2 
      may contribute to Pca development or progression are not known. We investigated 
      the expression of peroxisome proliferator-activated receptor (PPAR) gamma in 
      benign and malignant prostate tissues and the ability of 15S-HETE to activate 
      PPARgamma-dependent transcription and modulate proliferation of the Pca cell line 
      PC3. In contrast to benign prostate and similar to most Pca tissues, 15-LOX-2 
      mRNA was not detected in PC3 cells, and they did not produce detectable 15-HETE 
      from [14C]AA. By reverse transcription-PCR, PPARgamma mRNA was present in 18 of 
      18 benign and 9 of 9 tumor specimens. The PPARgamma ligand BRL 49653 and 15S-HETE 
      caused a dose-dependent inhibition of PC3 proliferation in a 14-day soft agar 
      colony-forming assay (IC50 of 3 and 30 microM, respectively). 15S-HETE (10 
      microM) caused greater inhibition than 10 microM 15R-HETE. At 3 days, BRL 49653 
      and 15S-HETE caused a slight increase in cells in G0-G1 and a corresponding 
      decrease in cells in S phase. In PC3 cells transiently transfected with a 
      luciferase reporter linked to a PPAR response element, 1 microM BRL 49653 and 10 
      microM 15S-HETE caused approximately threefold and greater than twofold induction 
      of PPAR-dependent transcription, respectively. By quantitative real-time reverse 
      transcription-PCR and Northern analysis, 3-day treatment with BRL 49653 and 
      15S-HETE caused a reduction of PPARgamma expression but a marked up-regulation of 
      the PPAR response element containing adipocyte type fatty acid binding protein. 
      These results support the hypothesis that 15-LOX-2-derived 15S-HETE may 
      constitute an endogenous ligand for PPARgamma in the prostate and that loss of 
      this pathway by reduced expression of 15-LOX-2 may contribute to increased 
      proliferation and reduced differentiation in prostate carcinoma.
FAU - Shappell, S B
AU  - Shappell SB
AD  - Department of Pathology, Vanderbilt University Medical Center, Nashville, 
      Tennessee 37232-2561, USA. scott.shappell@mcmail.vanderbilt.edu
FAU - Gupta, R A
AU  - Gupta RA
FAU - Manning, S
AU  - Manning S
FAU - Whitehead, R
AU  - Whitehead R
FAU - Boeglin, W E
AU  - Boeglin WE
FAU - Schneider, C
AU  - Schneider C
FAU - Case, T
AU  - Case T
FAU - Price, J
AU  - Price J
FAU - Jack, G S
AU  - Jack GS
FAU - Wheeler, T M
AU  - Wheeler TM
FAU - Matusik, R J
AU  - Matusik RJ
FAU - Brash, A R
AU  - Brash AR
FAU - Dubois, R N
AU  - Dubois RN
LA  - eng
GR  - CA58204/CA/NCI NIH HHS/United States
GR  - GM-53638/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Culture Media)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
RN  - 9002-18-0 (Agar)
RN  - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Agar/pharmacology
MH  - Arachidonate 15-Lipoxygenase/genetics/metabolism
MH  - Blotting, Northern
MH  - Catalysis
MH  - Cell Division/*drug effects
MH  - Culture Media/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/metabolism/*pharmacology
MH  - Isoenzymes/genetics/metabolism
MH  - Luciferases/drug effects/genetics/metabolism
MH  - Male
MH  - Prostatic Neoplasms/*genetics/pathology
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*genetics/metabolism
MH  - Recombinant Fusion Proteins/drug effects/genetics/metabolism
MH  - Rosiglitazone
MH  - Thiazoles/pharmacology
MH  - *Thiazolidinediones
MH  - Transcription Factors/*genetics/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
EDAT- 2001/02/24 12:00
MHDA- 2001/03/03 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Jan 15;61(2):497-503.