|
|
 Previous Article | Table of Contents | Next Article 
Altered expression of the retinoblastoma tumor-suppressor gene in leukemic
cell lines inhibits induction of differentiation but not G1- accumulation
G Bergh, M Ehinger, T Olofsson, B Baldetorp, E Johnsson, H Brycke, G Lindgren, I Olsson and U Gullberg
Department of Medicine, University of Lund, Sweden.
The retinoblastoma tumor-suppressor gene, RB, has been implicated in tumor
suppression, in regulation of the cell cycle, and in mediating cell
differentiation. RB is necessary for hematopoiesis in mice, and aberrant
RB-expression is associated with the progress and prognosis of leukemia. We
have used antisense oligonucleotides, established clones stably expressing
an antisense RB construct, and also established clones over expressing the
retinoblastoma protein (pRb) to study the role of RB expression in
monocytic differentiation induced by all-trans retinoic acid (ATRA) or
1-alpha-25-dihyroxycholecalciferol (Vit D3) in the monoblastic cell line
U-937 and erythroid differentiation induced by transforming growth factor
beta1 (TGFbeta1) and hemin in the erythroleukemic cell line K562. A
reduction in pRb production in antisense RB-transfected U-937 clones was
shown. Antisense oligonucleotides as well as expression of the antisense RB
construct suppressed differentiation responses to ATRA or Vit D3, as judged
by the capability to reduce nitro blue tetrazolium, by the appearance of
monocyte-related cell surface antigens and by morphologic criteria. K562
cells showed decreased differentiation response to TGFbeta1, but not to
hemin, when incubated with antisense oligonucleotides. U-937 antisense
RB-transfected cells were also suppressed in their ability to upregulate
levels of hypophosphorylated pRb when induced to differentiate. Although
U-937 cells incubated with antisense oligonucleotides and clones expressing
the antisense RB construct were hampered in their ability to differentiate
on incubation with ATRA or Vit D3, the induced G0/G1-accumulation was
similar to differentiating control cells treated with ATRA or Vit D3.
Intriguingly, U-937 clones overexpressing RB were also inhibited in their
differentiation response to ATRA or Vit D3 but not inhibited in their
ability to respond with G0/G1 accumulation when induced with these
substances. The results indicate that pRb plays a role in induced
differentiation of U-937 cells as well as K562 cells involving mechanisms
that, at least partially, are distinct from those inducing G1 accumulation.
Volume 89,
Issue 8,
pp. 2938-2950,
04/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Dimberg, F. Bahram, I. Karlberg, L.-G. Larsson, K. Nilsson, and F. Oberg
Retinoic acid-induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E and posttranscriptional up-regulation of p27Kip1
Blood,
March 15, 2002;
99(6):
2199 - 2206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Chylicki, M. Ehinger, H. Svedberg, and U. Gullberg
Characterization of the Molecular Mechanisms for p53-mediated Differentiation
Cell Growth Differ.,
November 1, 2000;
11(11):
561 - 571.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Chylicki, M. Ehinger, H. Svedberg, G. Bergh, I. Olsson, and U. Gullberg
p53-mediated Differentiation of the Erythroleukemia Cell Line K562
Cell Growth Differ.,
June 1, 2000;
11(6):
315 - 324.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Kanatani, T. Kasukabe, J. Okabe-Kado, Y. Yamamoto-Yamaguchi, N. Nagata, K. Motoyoshi, and Y. Honma
Role of CD14 Expression in the Differentiation-Apoptosis Switch in Human Monocytic Leukemia Cells Treated with 1{{alpha}},25-Dihydroxyvitamin D3 or Dexamethasone in the Presence of Transforming Growth Factor {beta}
Cell Growth Differ.,
October 1, 1999;
10(10):
705 - 712.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. Bergh, M. Ehinger, I. Olsson, S. E. W. Jacobsen, and U. Gullberg
Involvement of the Retinoblastoma Protein in Monocytic and Neutrophilic Lineage Commitment of Human Bone Marrow Progenitor Cells
Blood,
September 15, 1999;
94(6):
1971 - 1978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Liu, R. W. VanHoy, J. H. Zhou, R. Dantzer, G. G. Freund, and K. W. Kelley
Elevated Cyclin E Levels, Inactive Retinoblastoma Protein, and Suppression of the p27KIP1 Inhibitor Characterize Early Development of Promyeloid Cells into Macrophages
Mol. Cell. Biol.,
September 1, 1999;
19(9):
6229 - 6239.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tamir, J. Howard, R. R. Higgins, Y.-J. Li, L. Berger, E. Zacksenhaus, M. Reis, and Y. Ben-David
Fli-1, an Ets-Related Transcription Factor, Regulates Erythropoietin-Induced Erythroid Proliferation and Differentiation: Evidence for Direct Transcriptional Repression of the Rb Gene during Differentiation
Mol. Cell. Biol.,
June 1, 1999;
19(6):
4452 - 4464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Ketley, P. D. Allen, S. M. Kelsey, and A. C. Newland
Modulation of Idarubicin-Induced Apoptosis in Human Acute Myeloid Leukemia Blasts by All-Trans Retinoic Acid, 1,25(OH)2 Vitamin D3, and Granulocyte-Macrophage Colony-Stimulating Factor
Blood,
December 1, 1997;
90(11):
4578 - 4587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
