PMID- 9130711
OWN - NLM
STAT- MEDLINE
DCOM- 19970529
LR  - 20191210
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 16
IP  - 7
DP  - 1997 Apr 1
TI  - Modulation of retinoic acid sensitivity in lung cancer cells through dynamic 
      balance of orphan receptors nur77 and COUP-TF and their heterodimerization.
PG  - 1656-69
AB  - The diverse function of retinoic acid (RA) is mediated by its nuclear receptors, 
      the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). However, the 
      RA response is often lost in cancer cells that express the receptors. Previously, 
      it was demonstrated that the RA response is regulated by the COUP-TF orphan 
      receptors. Here, we present evidence that nur77, another orphan receptor whose 
      expression is highly induced by phorbol esters and growth factors, is involved in 
      modulation of the RA response. Expression of nur77 enhances ligand-independent 
      transactivation of RA response elements (RAREs) and desensitizes their RA 
      responsiveness. Conversely, expression of COUP-TF sensitizes RA responsiveness of 
      RAREs by repressing their basal transactivation activity. Unlike the effect of 
      COUP-TFs, the function of nur77 does not require direct binding of nur77 to the 
      RAREs, but is through interaction between nur77 and COUP-TFs. The interaction 
      occurs in solution and results in inhibition of COUP-TF RARE binding and 
      transcriptional activity. Unlike other nuclear receptors, a large portion of the 
      carboxy-terminal end of nur77 is not required for its interaction with COUP-TF. 
      In human lung cancer cell lines, COUP-TF is highly expressed in RA-sensitive cell 
      lines while nur77 expression is associated with RA resistance. Stable expression 
      of COUP-TF in nur77-positive, RA-resistant lung cancer cells enhances the 
      inducibility of RARbeta gene expression and growth inhibition by RA. These 
      observations demonstrate that a dynamic equilibrium between orphan receptors 
      nur77 and COUP-TF, through their heterodimerization that regulates COUP-TF RARE 
      binding, is critical for RA responsiveness of human lung cancer cells.
FAU - Wu, Q
AU  - Wu Q
AD  - The Burnham Institute, La Jolla Cancer Research Center, CA 92037, USA.
FAU - Li, Y
AU  - Li Y
FAU - Liu, R
AU  - Liu R
FAU - Agadir, A
AU  - Agadir A
FAU - Lee, M O
AU  - Lee MO
FAU - Liu, Y
AU  - Liu Y
FAU - Zhang, X
AU  - Zhang X
LA  - eng
GR  - CA51933/CA/NCI NIH HHS/United States
GR  - CA60988/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Antineoplastic Agents)
RN  - 0 (COUP Transcription Factor I)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NR2F1 protein, human)
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.5.1.18 (Glutathione Transferase)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*toxicity
MH  - Binding Sites
MH  - COUP Transcription Factor I
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/biosynthesis/drug effects/*physiology
MH  - Dimerization
MH  - Gene Expression/drug effects
MH  - Glutathione Transferase/biosynthesis
MH  - Humans
MH  - Lung Neoplasms
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Receptors, Cytoplasmic and Nuclear
MH  - Receptors, Glucocorticoid/physiology
MH  - Receptors, Steroid/physiology
MH  - Recombinant Fusion Proteins/drug effects/metabolism
MH  - Transcription Factors/biosynthesis/drug effects/*physiology
MH  - Transfection
MH  - Tretinoin/*toxicity
MH  - Tumor Cells, Cultured
PMC - PMC1169770
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
PMCR- 1998/04/01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
PHST- 1998/04/01 00:00 [pmc-release]
AID - 10.1093/emboj/16.7.1656 [doi]
PST - ppublish
SO  - EMBO J. 1997 Apr 1;16(7):1656-69. doi: 10.1093/emboj/16.7.1656.