PMID- 9344589
OWN - NLM
STAT- MEDLINE
DCOM- 19971125
LR  - 20131121
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 236
IP  - 1
DP  - 1997 Oct 10
TI  - Stable transfection of U937 cells with sense or antisense RXR-alpha cDNA suggests 
      a role for RXR-alpha in the control of monoblastic differentiation induced by 
      retinoic acid and vitamin D.
PG  - 94-102
AB  - Although retinoic acid (RA) has been known for many years to be a modulating 
      agent that plays a role in generating both granulocytes and monocytes, the 
      molecular mechanism underlying this role has not been defined in the monoblast 
      lineage. In particular, the part played by the retinoid X receptors (RXRs), which 
      are members of the steroid/thyroid hormone nuclear receptor family, has not been 
      explored. In this study, therefore, the human monoblastic leukemia cell line U937 
      has been used as a model system to investigate the role of one of the RXRs, 
      RXR-alpha, in monoblast differentiation. RXR-alpha mRNA was present in untreated 
      U937 cells, and levels increased after induction of differentiation with phorbol 
      ester. The same was found for RXR-beta mRNA. Using plasmids containing sense or 
      antisense RXR-alpha sequences under the control of an inducible promoter, we 
      generated stably transfected cell lines which expressed either increased or 
      decreased levels of RXR-alpha, respectively. The sense cell lines (U alpha S and 
      its clonal derivative alpha G2S) showed increased sensitivity to RA, while the 
      antisense cell lines (U alpha A and its clonal derivative alpha B5A) showed 
      decreased sensitivity to RA, as demonstrated by growth inhibition and by 
      regulation of an RA-responsive reporter gene. Both U alpha A and alpha B5A also 
      failed to respond to another modulating agent, 1 
      alpha,25-dihydroxycholecalciferol (DHCC), but only U alpha S and not alpha G2S 
      showed an enhanced response to DHCC. The combination of RA and DHCC together 
      inhibited growth of both sense and antisense cell lines. In addition, alpha G2S 
      exhibited increased expression of CD11b and CD54, while alpha B5A cells showed 
      increased expression of CD102, suggesting that RXR-alpha has a role in regulating 
      expression of cell adhesion molecules in U937 cells. These results demonstrate 
      that RXR-alpha has a role in mediating growth inhibition and cell adhesion during 
      myelomonocytic differentiation, and suggest that different species of 
      heterodimers involving RXR-alpha may control the acquisition of different 
      features of mature monocyte/macrophage function.
FAU - Brown, T R
AU  - Brown TR
AD  - Department of Molecular Pathology, University College London Medical School, 
      United Kingdom.
FAU - Stonehouse, T J
AU  - Stonehouse TJ
FAU - Branch, J S
AU  - Branch JS
FAU - Brickell, P M
AU  - Brickell PM
FAU - Katz, D R
AU  - Katz DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Antigens, CD)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DNA, Antisense)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ICAM2 protein, human)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 1406-16-2 (Vitamin D)
RN  - 5688UTC01R (Tretinoin)
RN  - FXC9231JVH (Calcitriol)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Antigens, CD/genetics
MH  - Antineoplastic Agents/*pharmacology
MH  - Calcitriol/pharmacology
MH  - Cell Adhesion Molecules/genetics
MH  - Cell Differentiation/drug effects/genetics
MH  - DNA, Antisense/*genetics
MH  - DNA-Binding Proteins/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Lymphoma, Large B-Cell, Diffuse
MH  - Macrophage-1 Antigen/genetics
MH  - Monocytes/cytology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Retinoic Acid/*genetics
MH  - Retinoid X Receptors
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/*genetics
MH  - Transfection
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured/chemistry/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Vitamin D/*pharmacology
EDAT- 1997/11/05 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/11/05 00:00
PHST- 1997/11/05 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/11/05 00:00 [entrez]
AID - S0014-4827(97)93704-6 [pii]
AID - 10.1006/excr.1997.3704 [doi]
PST - ppublish
SO  - Exp Cell Res. 1997 Oct 10;236(1):94-102. doi: 10.1006/excr.1997.3704.