PMID- 9199351
OWN - NLM
STAT- MEDLINE
DCOM- 19970724
LR  - 20231213
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 17
IP  - 7
DP  - 1997 Jul
TI  - Retinoid antagonism of NF-IL6: insight into the mechanism of antiproliferative 
      effects of retinoids in Kaposi's sarcoma.
PG  - 4159-68
AB  - All-trans-retinoic acid (RA) is active in the treatment of Kaposi's sarcoma (KS), 
      and retinoids inhibit KS cell growth in vitro. To understand the mechanism of 
      retinoid action in KS, we studied the expression of autocrine growth factors of 
      KS cells after RA treatment. We demonstrate that RA and its synthetic analogs 
      inhibit the proliferation of KS cells by inhibiting the mRNA and protein levels 
      of interleukin-6 (IL-6), an autocrine growth factor for KS cells. We further 
      demonstrate that nuclear retinoid receptors (RA receptors [RARs] and retinoid X 
      receptors [RXRs]) inhibit IL-6 promoter action by antagonizing the enhancer 
      action of NF-IL6, a basic domain leucine zipper transcription factor belonging to 
      the family of CAAT enhancer binding proteins. Furthermore, RARs and RXRs do not 
      bind in vitro to an NF-IL6 binding site. However, the secondary folded structure 
      of the DNA binding domain of RAR and RXR is obligatory for inhibiting NF-IL6 
      activity. Thus, NF-IL6 is a potential therapeutic target for the treatment of KS. 
      Finally, using receptor-selective synthetic retinoids, we demonstrate that NF-IL6 
      antagonism and transactivation are separable functions of RAR alpha, thus 
      indicating that synthetic retinoids with properties of NF-IL6 antagonism but 
      lacking transactivation capabilities can be synthesized. Such retinoids might 
      increase therapeutic potential in KS.
FAU - Nagpal, S
AU  - Nagpal S
AD  - Department of Biology, Allergan, Inc., Irvine, California 92713, USA.
FAU - Cai, J
AU  - Cai J
FAU - Zheng, T
AU  - Zheng T
FAU - Patel, S
AU  - Patel S
FAU - Masood, R
AU  - Masood R
FAU - Lin, G Y
AU  - Lin GY
FAU - Friant, S
AU  - Friant S
FAU - Johnson, A
AU  - Johnson A
FAU - Smith, D L
AU  - Smith DL
FAU - Chandraratna, R A
AU  - Chandraratna RA
FAU - Gill, P S
AU  - Gill PS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Growth Substances)
RN  - 0 (Interleukin-6)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
SB  - IM
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cell Division/drug effects
MH  - DNA-Binding Proteins/*antagonists & inhibitors
MH  - Gene Expression Regulation, Neoplastic
MH  - Growth Inhibitors/pharmacology
MH  - Growth Substances/physiology
MH  - Humans
MH  - Interleukin-6/physiology
MH  - Nuclear Proteins/*antagonists & inhibitors
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - RNA, Neoplasm/genetics
MH  - Receptors, Retinoic Acid/genetics/physiology
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Sarcoma, Kaposi/*pathology
MH  - Signal Transduction
MH  - Transcription Factors/physiology
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Retinoic Acid Receptor gamma
PMC - PMC232269
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
PMCR- 1997/07/01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
PHST- 1997/07/01 00:00 [pmc-release]
AID - 10.1128/MCB.17.7.4159 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1997 Jul;17(7):4159-68. doi: 10.1128/MCB.17.7.4159.