PMID- 10629053
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 3
DP  - 2000 Feb
TI  - Orphan receptor COUP-TF is required for induction of retinoic acid receptor beta, 
      growth inhibition, and apoptosis by retinoic acid in cancer cells.
PG  - 957-70
AB  - Retinoic acid receptor beta (RARbeta) plays a critical role in mediating the 
      anticancer effects of retinoids. Expression of RARbeta is highly induced by 
      retinoic acid (RA) through a RA response element (betaRARE) that is activated by 
      heterodimers of RARs and retinoid X receptors (RXRs). However, RARbeta induction 
      is often lost in cancer cells despite expression of RARs and RXRs. In this study, 
      we provide evidence that orphan receptor COUP-TF is required for induction of 
      RARbeta expression, growth inhibition, and apoptosis by RA in cancer cells. 
      Expression of COUP-TF correlates with RARbeta induction in a variety of cancer 
      cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer 
      cells restores induction of RARbeta expression, growth inhibition, and apoptosis 
      by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA 
      represses the RA effects. In a transient transfection assay, COUP-TF strongly 
      induced transcriptional activity of the RARbeta promoter in a RA- and 
      RARalpha-dependent manner. By mutation analysis, we demonstrate that the effect 
      of COUP-TF requires its binding to a DR-8 element present in the RARbeta 
      promoter. The binding of COUP-TF to the DR-8 element synergistically increases 
      the RA-dependent RARalpha transactivation function by enhancing the interaction 
      of RARalpha with its coactivator CREB binding protein. These results demonstrate 
      that COUP-TF, by serving as an accessory protein for RARalpha to induce RARbeta 
      expression, plays a critical role in regulating the anticancer activities of 
      retinoids.
FAU - Lin, B
AU  - Lin B
AD  - Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
FAU - Chen, G Q
AU  - Chen GQ
FAU - Xiao, D
AU  - Xiao D
FAU - Kolluri, S K
AU  - Kolluri SK
FAU - Cao, X
AU  - Cao X
FAU - Su, H
AU  - Su H
FAU - Zhang, X K
AU  - Zhang XK
LA  - eng
GR  - R01 CA060988/CA/NCI NIH HHS/United States
GR  - CA51933/CA/NCI NIH HHS/United States
GR  - CA60988/CA/NCI 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  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (COUP Transcription Factor I)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NR2F1 protein, human)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Base Sequence
MH  - Binding Sites
MH  - Breast Neoplasms
MH  - COUP Transcription Factor I
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dimerization
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Kinetics
MH  - Mutagenesis, Site-Directed
MH  - Promoter Regions, Genetic
MH  - Receptors, Glucocorticoid/metabolism
MH  - Receptors, Retinoic Acid/biosynthesis/*genetics
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Transcription Factors/genetics/*metabolism
MH  - Transfection
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC85213
EDAT- 2000/01/11 09:00
MHDA- 2000/02/19 09:00
PMCR- 2000/02/01
CRDT- 2000/01/11 09:00
PHST- 2000/01/11 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/11 09:00 [entrez]
PHST- 2000/02/01 00:00 [pmc-release]
AID - 1474 [pii]
AID - 10.1128/MCB.20.3.957-970.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Feb;20(3):957-70. doi: 10.1128/MCB.20.3.957-970.2000.