PMID- 8877104
OWN - NLM
STAT- MEDLINE
DCOM- 19970114
LR  - 20131121
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 7
IP  - 9
DP  - 1996 Sep
TI  - Vitamin D3- and retinoic acid-induced monocytic differentiation: interactions 
      between the endogenous vitamin D3 receptor, retinoic acid receptors, and retinoid 
      X receptors in U-937 cells.
PG  - 1239-49
AB  - Retinoic acid (RA) and 1,25 alpha-dihydroxycholecalciferol (VitD3) are potent 
      regulators of hematopoletic differentiation. Yet, little is known as to how the 
      RA and VitD3 receptor network operates in hematopoietic cells, and whether 
      receptor interactions can explain the interplay between the RA- and 
      VitD3-signaling pathways during differentiation. Therefore, we analyzed the 
      expression, DNA binding, and transcriptional activity of the endogenous RA and 
      VitD3 receptors [retinoic acid receptors (RARs), retinoid X receptors (RXRs), and 
      VitD3 receptor (VDR)] in the U-937 cell line, in which RA and VitD3 induce 
      distinct monocytic differentiation pathways. VitD3 induction resulted in the 
      formation of VDR/RXR DNA-binding complexes on both VitD3 response elements and RA 
      response elements (RAREs). However, transcriptional activation was only observed 
      from a VitD3 response element-driven reporter construct. Several DNA-binding 
      complexes were detected on RAREs in undifferentiated cells. Stimulation by RA 
      resulted in increased RAR beta/RXR DNA binding, activated RARE-dependent 
      transcription, and increased expression of RAR-beta. Concomitant stimulation by 
      VitD3 inhibited the RA-stimulated formation of RAR beta/RXR heterodimers, 
      favoring VDR/RXR binding to the RARE. Also, VitD3 inhibited the expression of 
      CD23 and CD49f, characteristic markers of retinoid-induced U-937 cell 
      differentiation. In contrast, neither the RA-stimulated, RARE-mediated 
      transcription nor the induced RAR-beta expression was suppressed by VitD3, 
      suggesting that VitD3 selectively inhibited the retinoid-induced differentiation 
      program but not the RARE-mediated signal. These results demonstrate a complex 
      role for VitD3 in modifying the retinoid differentiation pathway and may have 
      implications for differentiation-inducing therapy of hematopoietic tumors.
FAU - Botling, J
AU  - Botling J
AD  - Department of Pathology, Uppsala University, Sweden.
FAU - Oberg, F
AU  - Oberg F
FAU - Torma, H
AU  - Torma H
FAU - Tuohimaa, P
AU  - Tuohimaa P
FAU - Blauer, M
AU  - Blauer M
FAU - Nilsson, K
AU  - Nilsson K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 0 (Cell Extracts)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (retinoic acid receptor beta)
RN  - 1C6V77QF41 (Cholecalciferol)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - Cell Extracts
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cholecalciferol/pharmacology
MH  - DNA/genetics/metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Interphase
MH  - Monocytes/*cytology/metabolism
MH  - RNA, Messenger/analysis
MH  - Receptors, Calcitriol/genetics/*metabolism
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Recombinant Fusion Proteins
MH  - Retinoid X Receptors
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation/*drug effects/physiology
MH  - Tretinoin/pharmacology
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1996 Sep;7(9):1239-49.