PMID- 9343423
OWN - NLM
STAT- MEDLINE
DCOM- 19971121
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 17
IP  - 11
DP  - 1997 Nov
TI  - Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by 
      retinoid X receptor-selective retinoids.
PG  - 6598-608
AB  - All-trans-retinoic acid (trans-RA) and other retinoids exert anticancer effects 
      through two types of retinoid receptors, the RA receptors (RARs) and retinoid X 
      receptors (RXRs). Previous studies demonstrated that the growth-inhibitory 
      effects of trans-RA and related retinoids are impaired in certain 
      estrogen-independent breast cancer cell lines due to their lower levels of RAR 
      alpha and RARbeta. In this study, we evaluated several synthetic retinoids for 
      their ability to induce growth inhibition and apoptosis in both 
      trans-RA-sensitive and trans-RA-resistant breast cancer cell lines. Our results 
      demonstrate that RXR-selective retinoids, particularly in combination with 
      RAR-selective retinoids, could significantly induce RARbeta and inhibit the 
      growth and induce the apoptosis of trans-RA-resistant, RAR alpha-deficient 
      MDA-MB-231 cells but had low activity against trans-RA-sensitive ZR-75-1 cells 
      that express high levels of RAR alpha. Using gel retardation and transient 
      transfection assays, we found that the effects of RXR-selective retinoids on 
      MDA-MB-231 cells were most likely mediated by RXR-nur77 heterodimers that bound 
      to the RA response element in the RARbeta promoter and activated the RARbeta 
      promoter in response to RXR-selective retinoids. In contrast, growth inhibition 
      by RAR-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most 
      probably occurred through RXR-RAR alpha heterodimers that also bound to and 
      activated the RARbeta promoter. In MDA-MB-231 clones stably expressing RAR alpha, 
      both RARbeta induction and growth inhibition by RXR-selective retinoids were 
      suppressed, while the effects of RAR-selective retinoids were enhanced. Together, 
      our results demonstrate that activation of RXR can inhibit the growth of 
      trans-RA-resistant MDA-MB-231 breast cancer cells and suggest that low cellular 
      RAR alpha may regulate the signaling switch from RAR-mediated to RXR-mediated 
      growth inhibition in breast cancer cells.
FAU - Wu, Q
AU  - Wu Q
AD  - The Burnham Institute, La Jolla Cancer Research Center, California 92037, USA.
FAU - Dawson, M I
AU  - Dawson MI
FAU - Zheng, Y
AU  - Zheng Y
FAU - Hobbs, P D
AU  - Hobbs PD
FAU - Agadir, A
AU  - Agadir A
FAU - Jong, L
AU  - Jong L
FAU - Li, Y
AU  - Li Y
FAU - Liu, R
AU  - Liu R
FAU - Lin, B
AU  - Lin B
FAU - Zhang, X K
AU  - Zhang XK
LA  - eng
GR  - CA51933/CA/NCI NIH HHS/United States
GR  - CA60988/CA/NCI NIH HHS/United States
PT  - Comparative Study
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 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Binding, Competitive
MH  - Breast Neoplasms/*metabolism
MH  - Cell Division/drug effects
MH  - DNA-Binding Proteins/metabolism
MH  - Drug Resistance
MH  - Evaluation Studies as Topic
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Isomerism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Receptors, Cytoplasmic and Nuclear
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Receptors, Steroid
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Signal Transduction/drug effects
MH  - Transcription Factors/*metabolism
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC232513
EDAT- 1997/10/29 00:00
MHDA- 1997/10/29 00:01
PMCR- 1997/11/01
CRDT- 1997/10/29 00:00
PHST- 1997/10/29 00:00 [pubmed]
PHST- 1997/10/29 00:01 [medline]
PHST- 1997/10/29 00:00 [entrez]
PHST- 1997/11/01 00:00 [pmc-release]
AID - 10.1128/MCB.17.11.6598 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1997 Nov;17(11):6598-608. doi: 10.1128/MCB.17.11.6598.