|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1957-1966
The Zinc Finger Transcription Factor Egr-1 Activates Macrophage
Differentiation in M1 Myeloblastic Leukemia Cells
Kandasamy Krishnaraju,
Barbara Hoffman, and
Dan A. Liebermann
From the Fels Institute for Cancer Research and Molecular Biology,
and Department of Biochemistry, Temple University School of Medicine,
Philadelphia, PA.
We previously have shown that the zinc finger transcription factor
Egr-1 blocked granulocytic differentiation of HL-60 cells, restricting
differentiation along the monocytic lineage. Egr-1 also was observed to
block granulocyte colony-stimulating factor (G-CSF)-induced
differentiation of interleukin-3 (IL-3)-dependent 32Dcl3 hematopoietic
precursor cells, endowing the cells with the ability to be induced by
granulocyte-macrophage colony-stimulating factor (GM-CSF) for terminal
differentiation along the macrophage lineage. To better understand the
function of Egr-1 as a positive modulator of monocytic differentiation,
in this work we have studied the effect of ectopic expression of Egr-1
on the murine myeloblastic leukemic cell line M1, which is induced for
differentiation by the physiological inducer IL-6. It is shown that,
unlike in HL-60 and 32Dcl3 cells, ectopic expression of Egr-1 in M1
cells resulted in activation of the macrophage differentiation program
in the absence of differentiation inducer. This included the appearance of morphologically differentiated cells, decreased growth rate in mass
culture, and cloning efficiency in soft agar, and expression of
endogenous c-myb and c-myc mRNAs was markedly
downregulated. Untreated M1Egr-1 cells also exhibited cell adherence,
expression of Fc and C3 receptors, and upregulation of the myeloid
differentiation primary response genes c-Jun, junD, and
junB and the late genetic markers ferritin light-chain
and lysozyme. Ectopic expression of Egr-1 in M1 cells also
dramatically increased the sensitivity of the cells for IL-6-induced
differentiation, allowed a higher proportion of M1 cells to become
terminally differentiated under conditions of optimal stimulation for
differentiation, and decreased M1 leukemogenicity in vivo. These
findings demonstrate that the functions of Egr-1 as a positive
modulator of macrophage differentiation vary, depending on the state of
lineage commitment for differentiation of the hematopoietic cell type.
© 1998 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:
|
|
|
|
 
J. H. Carter and W. G. Tourtellotte
Early Growth Response Transcriptional Regulators Are Dispensable for Macrophage Differentiation
J. Immunol.,
March 1, 2007;
178(5):
3038 - 3047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Schippert, E. Burkhardt, M. Feldkaemper, and F. Schaeffel
Relative Axial Myopia in Egr-1 (ZENK) Knockout Mice
Invest. Ophthalmol. Vis. Sci.,
January 1, 2007;
48(1):
11 - 17.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Li, M. R. Power, and T.-J. Lin
De novo synthesis of early growth response factor-1 is required for the full responsiveness of mast cells to produce TNF and IL-13 by IgE and antigen stimulation
Blood,
April 1, 2006;
107(7):
2814 - 2820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dauffy, G. Mouchiroud, and R. P. Bourette
The interferon-inducible gene, Ifi204, is transcriptionally activated in response to M-CSF, and its expression favors macrophage differentiation in myeloid progenitor cells
J. Leukoc. Biol.,
January 1, 2006;
79(1):
173 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E Garnett, P. Chapman, J. A Chambers, I. D Waddell, and D. S W Boam
Differential gene expression between Zucker Fatty rats and Zucker Diabetic Fatty rats: a potential role for the immediate-early gene Egr-1 in regulation of beta cell proliferation
J. Mol. Endocrinol.,
August 1, 2005;
35(1):
13 - 25.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shafarenko, D. A. Liebermann, and B. Hoffman
Egr-1 abrogates the block imparted by c-Myc on terminal M1 myeloid differentiation
Blood,
August 1, 2005;
106(3):
871 - 878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Singh, J. Svaren, J. Grayson, and M. Suresh
CD8 T Cell Responses to Lymphocytic Choriomeningitis Virus in Early Growth Response Gene 1-Deficient Mice
J. Immunol.,
September 15, 2004;
173(6):
3855 - 3862.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zheng, R. Ravatn, Y. Lin, W.-C. Shih, A. Rabson, R. Strair, E. Huberman, A. Conney, and K.-V. Chin
Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis
Nucleic Acids Res.,
October 15, 2002;
30(20):
4489 - 4499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Carleton, M. C. Haks, S. A. A. Smeele, A. Jones, S. M. Belkowski, M. A. Berger, P. Linsley, A. M. Kruisbeek, and D. L. Wiest
Early Growth Response Transcription Factors Are Required for Development of CD4-CD8- Thymocytes to the CD4+CD8+ Stage
J. Immunol.,
February 15, 2002;
168(4):
1649 - 1658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Danilenko, X. Wang, and G. P. Studzinski
Carnosic Acid and Promotion of Monocytic Differentiation of HL60-G Cells Initiated by Other Agents
J Natl Cancer Inst,
August 15, 2001;
93(16):
1224 - 1233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Krishnaraju, B. Hoffman, and D. A. Liebermann
Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages
Blood,
March 1, 2001;
97(5):
1298 - 1305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Aoki, S. Kimura, Y. Takiyama, Y. Atsuta, A. Abe, K. Sato, and M. Katagiri
The Role of the DAP12 Signal in Mouse Myeloid Differentiation
J. Immunol.,
October 1, 2000;
165(7):
3790 - 3796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Akuzawa, M. Kurabayashi, Y. Ohyama, M. Arai, and R. Nagai
Zinc Finger Transcription Factor Egr-1 Activates Flt-1 Gene Expression in THP-1 Cells on Induction for Macrophage Differentiation
Arterioscler. Thromb. Vasc. Biol.,
February 1, 2000;
20(2):
377 - 384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Mora-Garcia and K. M. Sakamoto
Granulocyte Colony-stimulating Factor Induces egr-1 Up-regulation through Interaction of Serum Response Element-binding Proteins
J. Biol. Chem.,
July 14, 2000;
275(29):
22418 - 22426.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
