PMID- 8634418
OWN - NLM
STAT- MEDLINE
DCOM- 19960710
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 87
IP  - 5
DP  - 1996 Mar 1
TI  - The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth 
      inhibition of human CD34+ erythroid progenitor cells.
PG  - 1728-36
AB  - Previous studies have shown that retinoic acid (RA), similar to tumor necrosis 
      factor-alpha (TNF-alpha), can act as a bifunctional regulator of the growth of 
      bone marrow progenitors, in that it can stimulate granulocyte-macrophage 
      colony-stimulating factor (GM-CSF)- or interleukin-3 (IL-3)-induced GM colony 
      formation, but potently inhibit G-CSF-induced growth. The present study, using 
      highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells, 
      demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming 
      unit-erythroid (BFU-E) colony formation regardless of the cytokine stimulating 
      growth. Specifically, 9-cis-RA potently inhibited the growth of BFU-E response to 
      erythropoietin (Epo) (100%), stem cell factor (SCF) + Epo (92%), IL-3 + Epo 
      (97%), IL-4 + Epo (88%), and IL-9 + Epo (100%). Erythroid colony growth was also 
      inhibited when CD34+ progenitors were seeded at one cell per well, suggesting a 
      direct action of RA. Using synthetic ligands to retinoic acid receptors (RARs) 
      and retinoid X receptors (RXRs) that selectively bind and activate RAR-RXR or 
      RXR-RXR dimers, respectively, we dissected the involvement of the two retinoid 
      response pathways in the regulation of normal myeloid and erythroid progenitor 
      cell growth. Transactivation studies showed that both the RAR (Ro 13-7410) and 
      RXR (Ro 25-6603 and Ro 25-7386) ligands were highly selective at 100 nmol/L. At 
      this concentration, Ro 13-7410 potently inhibited G-CSF-stimulated myeloid as 
      well as SCF + Epo-induced erythroid colony growth. At the same concentration, Ro 
      25-6603 and Ro 25-7386 had little or no effect on G-CSF-induced colony formation, 
      whereas they inhibited 75% and 53%, respectively, of SCF + Epo-stimulated BFU-E 
      colony growth. Thus, the RAR-RXR response pathway can signal growth inhibition of 
      normal bone marrow myeloid and erythroid progenitor cells. In addition, we 
      demonstrate a unique involvement of the RXR-RXR pathway in mediating growth 
      inhibition of erythroid but not myeloid progenitor cells.
FAU - Rusten, L S
AU  - Rusten LS
AD  - Department of Immunology, Institute for Cancer Research, The Norweigian Radium 
      Hospital, Oslo.
FAU - Dybedal, I
AU  - Dybedal I
FAU - Blomhoff, H K
AU  - Blomhoff HK
FAU - Blomhoff, R
AU  - Blomhoff R
FAU - Smeland, E B
AU  - Smeland EB
FAU - Jacobsen, S E
AU  - Jacobsen SE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD34)
RN  - 0 (Benzoates)
RN  - 0 (Cyclohexanes)
RN  - 0 (Hematopoietic Cell Growth Factors)
RN  - 0 (Interleukins)
RN  - 0 (Pentanoic Acids)
RN  - 0 (RARA protein, human)
RN  - 0 (Rara protein, mouse)
RN  - 0 (Rara protein, rat)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Ro 25-6603)
RN  - 0 (Stem Cell Factor)
RN  - 0 (Transcription Factors)
RN  - 11096-26-7 (Erythropoietin)
RN  - 5688UTC01R (Tretinoin)
RN  - 71441-28-6 
      (4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic 
      acid)
SB  - IM
MH  - Animals
MH  - Antigens, CD34
MH  - Base Sequence
MH  - Benzoates/pharmacology
MH  - Consensus Sequence
MH  - Cyclohexanes/pharmacology
MH  - Depression, Chemical
MH  - Erythroid Precursor Cells/*cytology/drug effects
MH  - Erythropoiesis/*drug effects
MH  - Erythropoietin/pharmacology
MH  - Hematopoietic Cell Growth Factors/pharmacology
MH  - Humans
MH  - Interleukins/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Pentanoic Acids/pharmacology
MH  - Rats
MH  - Receptors, Retinoic Acid/agonists/drug effects/*physiology
MH  - Recombinant Proteins/pharmacology
MH  - Retinoic Acid Receptor alpha
MH  - Retinoid X Receptors
MH  - Retinoids/pharmacology
MH  - Signal Transduction/*physiology
MH  - Stem Cell Factor/pharmacology
MH  - Transcription Factors/drug effects/*physiology
MH  - Tretinoin/pharmacology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - S0006-4971(20)65280-6 [pii]
PST - ppublish
SO  - Blood. 1996 Mar 1;87(5):1728-36.