PMID- 9228081
OWN - NLM
STAT- MEDLINE
DCOM- 19970909
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 30
DP  - 1997 Jul 25
TI  - Specific activation of retinoic acid receptors (RARs) and retinoid X receptors 
      reveals a unique role for RARgamma in induction of differentiation and apoptosis 
      of S91 melanoma cells.
PG  - 18990-9
AB  - Retinoic acid (RA) and 9-cis-RA induce growth arrest and differentiation of S91 
      melanoma cells. RA activates retinoic acid receptors (RARs), whereas 9-cis-RA 
      activates both RARs and retinoid X receptors (RXRs). Both classes of receptors 
      function as ligand-dependent transcription factors. S91 melanoma cells contain 
      mRNA for RXRalpha, RXRbeta, RARalpha, RARgamma, and RARbeta in low levels. Among 
      these, only RARbeta gene transcription is induced by retinoids. However, at 
      present the individual role(s) for each RXR and RAR isoform in these processes is 
      unclear. We assessed the function of all isoforms in the S91 melanoma model by 
      using RXR and RAR isoform-specific retinoids to study their effects on cell 
      growth, RARbeta expression, and differentiation. Activation of each of the 
      endogenous RXR or RAR isoforms induces RARbeta gene expression, and blocks 
      cellular proliferation. However, only the RARgamma-ligands cause additional 
      differentiation toward a melanocytic phenotype, which coincides with substantial 
      apoptosis well before morphological changes are apparent. Apoptosis is completely 
      dependent on de novo protein synthesis but cannot be induced by changes in 
      activities of AP-1, protein kinase C, and protein kinase A, nor can it be blocked 
      by the presence of the antioxidant glutathione. These results argue against a 
      specific role for RARbeta, but suggest that RARgamma has a critical role in a 
      genetic switch between melanocytes and melanoma, and induction of 
      ligand-dependent apoptosis.
FAU - Spanjaard, R A
AU  - Spanjaard RA
AD  - Department of Surgery, Division of Surgical Oncology, Laboratory of Biologic 
      Cancer Therapy, Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Ikeda, M
AU  - Ikeda M
FAU - Lee, P J
AU  - Lee PJ
FAU - Charpentier, B
AU  - Charpentier B
FAU - Chin, W W
AU  - Chin WW
FAU - Eberlein, T J
AU  - Eberlein TJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ligands)
RN  - 0 (Melanins)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Cell Differentiation/*physiology
MH  - Gene Expression
MH  - Glutathione/metabolism
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Melanins/biosynthesis
MH  - Melanoma
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - Receptors, Retinoic Acid/genetics/*metabolism/*physiology
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - Retinoic Acid Receptor gamma
EDAT- 1997/07/25 00:00
MHDA- 1997/07/25 00:01
CRDT- 1997/07/25 00:00
PHST- 1997/07/25 00:00 [pubmed]
PHST- 1997/07/25 00:01 [medline]
PHST- 1997/07/25 00:00 [entrez]
AID - S0021-9258(18)39079-3 [pii]
AID - 10.1074/jbc.272.30.18990 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Jul 25;272(30):18990-9. doi: 10.1074/jbc.272.30.18990.