|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2369-2379
Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway
Correlates With Growth Factor Independence of Megakaryocytic
Leukemic Cell Lines
Richard Y. Liu,
Chun Fan,
Roy Garcia,
Richard Jove, and
Kenneth S. Zuckerman
From the Division of Medical Oncology and Hematology, the Department
of Internal Medicine and the Department of Biochemistry and Molecular
Biology, University of South Florida College of Medicine, and Molecular
Oncology and Hematologic Malignancy Programs, H. Lee Moffitt Cancer
Center and Research Institute, Tampa, FL.
The factor-independent Dami/HEL and Meg-01 and factor-dependent Mo7e
leukemic cell lines were used as models to investigate JAK/STAT signal
transduction pathways in leukemic cell proliferation. Although Dami/HEL
and Meg-01 cell proliferation in vitro was independent of and
unresponsive to exogenous cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), and tumor necrosis factor-
(TNF-), the growth of Mo7e cells was dependent on hematopoietic
growth factors. When these cell lines were cultured in medium without
cytokines, a constitutively activated STAT-like DNA-binding factor was
detected in nuclear extracts from both Dami/HEL and Meg-01 cells.
However, the STAT-like factor was not detectable in untreated Mo7e
cells, but was activated transiently in Mo7e cells in response to
cytokine treatments. The constitutively activated and cytokine-induced STAT-like DNA-binding factor in these three cell lines was identified as STAT5 by oligonucleotide competition gel mobility assays and by
specific anti-STAT antibody gel supershift assays. Constitutive activation of JAK2 also was detected in the factor-independent cell
lines, but not in Mo7e cells without cytokine exposure. Meg-01 cells
express a p185 BCR/ABL oncogene, which may be responsible for the
constitutive activation of STAT5. Dami/HEL cells do not express the
BCR/ABL oncogene, but increased constitutive phosphorylation of Raf-1
oncoprotein was detected. In cytokine bioassays using growth
factor-dependent Mo7e and TF-1 cells as targets, conditioned media from
Dami/HEL and Meg-01 cells did not show stimulatory effects on cell
proliferation. Our results indicate that the constitutive activation of
JAK2/STAT5 correlates with the factor-independent growth of Dami/HEL
and Meg-01 cells. The constitutive activation of JAK2/STAT5 in Dami/HEL
cells is triggered by a mechanism other than autocrine cytokines or the
BCR/ABL oncoprotein.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Frohling, D. B. Lipka, S. Kayser, C. Scholl, R. F. Schlenk, H. Dohner, D. G. Gilliland, R. L. Levine, and K. Dohner
Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7
Blood,
February 1, 2006;
107(3):
1242 - 1243.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shi, J. C. Cooper, and C.-L. Yu
A Constitutively Active Lck Kinase Promotes Cell Proliferation and Resistance to Apoptosis through Signal Transducer and Activator of Transcription 5b Activation
Mol. Cancer Res.,
January 1, 2006;
4(1):
39 - 45.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Estes, Y. Ozawa, A. H. Williams, A. F. List, and L. Sokol
Homozygous JAK2 V617P Gain-of-Function Mutation Is Responsible for Constitutive JAK2/STAT5 Activation and Proliferation of HEL.92.1.7. Cell Line.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
4377 - 4377.
[Abstract]
|
|
|
|
|
|
|
V. Moucadel and S. N. Constantinescu
Differential STAT5 Signaling by Ligand-dependent and Constitutively Active Cytokine Receptors
J. Biol. Chem.,
April 8, 2005;
280(14):
13364 - 13373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Golas, K. Arndt, C. Etienne, J. Lucas, D. Nardin, J. Gibbons, P. Frost, F. Ye, D. H. Boschelli, and F. Boschelli
SKI-606, a 4-Anilino-3-quinolinecarbonitrile Dual Inhibitor of Src and Abl Kinases, Is a Potent Antiproliferative Agent against Chronic Myelogenous Leukemia Cells in Culture and Causes Regression of K562 Xenografts in Nude Mice
Cancer Res.,
January 15, 2003;
63(2):
375 - 381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Burdelya, R. Catlett-Falcone, A. Levitzki, F. Cheng, L. B. Mora, E. Sotomayor, D. Coppola, J. Sun, S. Sebti, W. S. Dalton, et al.
Combination Therapy with AG-490 and Interleukin 12 Achieves Greater Antitumor Effects than Either Agent Alone
Mol. Cancer Ther.,
September 1, 2002;
1(11):
893 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kijowski, M. Baj-Krzyworzeka, M. Majka, R. Reca, L. A. Marquez, M. Christofidou-Solomidou, A. Janowska-Wieczorek, and M. Z. Ratajczak
The SDF-1-CXCR4 Axis Stimulates VEGF Secretion and Activates Integrins but does not Affect Proliferation and Survival in Lymphohematopoietic Cells
Stem Cells,
September 1, 2001;
19(5):
453 - 466.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Eisbacher, L. M. Khachigian, T. H. Khin, M. L. Holmes, and B. H. Chong
Inducible Expression of the Megakarocyte-specific Gene Glycoprotein IX Is Mediated through an Ets Binding Site and Involves Upstream Activation of Extracellular Signal-regulated Kinase
Cell Growth Differ.,
August 1, 2001;
12(8):
435 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Friedrichsen, E. D. Galsgaard, J. H. Nielsen, and A. Møldrup
Growth Hormone- and Prolactin-Induced Proliferation of Insulinoma Cells, INS-1, Depends on Activation of STAT5 (Signal Transducer and Activator of Transcription 5)
Mol. Endocrinol.,
January 1, 2001;
15(1):
136 - 148.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Majka, A. Janowska-Wieczorek, J. Ratajczak, M. A. Kowalska, G. Vilaire, Z. K. Pan, M. Honczarenko, L. A. Marquez, M. Poncz, and M. Z. Ratajczak
Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis
Blood,
December 15, 2000;
96(13):
4142 - 4151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Di Bacco, K. Keeshan, S. L. McKenna, and T. G. Cotter
Molecular Abnormalities in Chronic Myeloid Leukemia: Deregulation of Cell Growth and Apoptosis
Oncologist,
October 1, 2000;
5(5):
405 - 415.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. C. Ward, I. Touw, and A. Yoshimura
The Jak-Stat pathway in normal and perturbed hematopoiesis
Blood,
January 1, 2000;
95(1):
19 - 29.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Y. Liu, C. Fan, N. E. Olashaw, X. Wang, and K. S. Zuckerman
Tumor Necrosis Factor-alpha -induced Proliferation of Human Mo7e Leukemic Cells Occurs via Activation of Nuclear Factor kappa B Transcription Factor
J. Biol. Chem.,
May 14, 1999;
274(20):
13877 - 13885.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
