CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Matikainen, S.
Right arrow Articles by Julkunen, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matikainen, S.
Right arrow Articles by Julkunen, I.

Cell Growth & Differentiation, Vol 8, Issue 6 687-698, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Retinoic acid induces signal transducer and activator of transcription (STAT) 1, STAT2, and p48 expression in myeloid leukemia cells and enhances their responsiveness to interferons

S Matikainen, T Ronni, A Lehtonen, T Sareneva, K Melen, S Nordling, DE Levy and I Julkunen
National Public Health Institute, Helsinki, Finland.

IFNs are antiproliferative cytokines that have growth-inhibitory effects on various normal and malignant cells. Therefore, they have been used in the treatment of certain forms of cancer, such as chronic myelogenous leukemia and hairy cell leukemia. However, there is little evidence that IFNs would be effective in the treatment of acute myelogenous leukemia, and molecular mechanisms underlying IFN unresponsiveness have not been clarified. Here we have studied the activation and induction of IFN-specific transcription factors signal transducer and activator of transcription (STAT) 1, STAT2, and p48 in all-trans-retinoic acid (ATRA)-differentiated myeloid leukemia cells using promyelocytic NB4, myeloblastic HL-60, and monoblastic U937 cells as model systems. These cells respond to ATRA by growth inhibition and differentiation. We show that in undifferentiated NB4 cells, 2',5'-oligoadenylate synthetase and MxB gene expression is not activated by IFN-alpha, possibly due to a relative lack of signaling molecules, especially p48 protein. However, during ATRA-induced differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and corresponding protein levels were elevated both in NB4 and U937 cells, apparently correlating to an enhanced responsiveness of these cells to IFNs. ATRA treatment of NB4 cells sensitized them to IFN action as seen by increased IFN-gamma activation site DNA-binding activity or by efficient formation of IFN-alpha-specific ISGF3 complex and subsequent oligoadenylate synthetase and MxB gene expression. Lack of p48 expression could be one of the mechanisms of promyelocytic leukemia cell escape from growth-inhibitory effects of IFN-alpha.


This article has been cited by other articles:


Home page
JCOHome page
M. Benekli, H. Baumann, and M. Wetzler
Targeting Signal Transducer and Activator of Transcription Signaling Pathway in Leukemias
J. Clin. Oncol., September 10, 2009; 27(26): 4422 - 4432.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
E. Parrella, M. Gianni', V. Cecconi, E. Nigro, M. M. Barzago, A. Rambaldi, C. Rochette-Egly, M. Terao, and E. Garattini
Phosphodiesterase IV Inhibition by Piclamilast Potentiates the Cytodifferentiating Action of Retinoids in Myeloid Leukemia Cells: CROSS-TALK BETWEEN THE cAMP AND THE RETINOIC ACID SIGNALING PATHWAYS
J. Biol. Chem., October 1, 2004; 279(40): 42026 - 42040.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
N. Clarke, A. M. Jimenez-Lara, E. Voltz, and H. Gronemeyer
Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL
EMBO J., August 4, 2004; 23(15): 3051 - 3060.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
L. Klampfer, J. Huang, G. Corner, J. Mariadason, D. Arango, T. Sasazuki, S. Shirasawa, and L. Augenlicht
Oncogenic Ki-Ras Inhibits the Expression of Interferon-responsive Genes through Inhibition of STAT1 and STAT2 Expression
J. Biol. Chem., November 21, 2003; 278(47): 46278 - 46287.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
S. Kambhampati, Y. Li, A. Verma, A. Sassano, B. Majchrzak, D. K. Deb, S. Parmar, N. Giafis, D. V. Kalvakolanu, A. Rahman, et al.
Activation of Protein Kinase C{delta} by All-trans-retinoic Acid
J. Biol. Chem., August 29, 2003; 278(35): 32544 - 32551.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Dimberg, I. Karlberg, K. Nilsson, and F. Oberg
Ser727/Tyr701-phosphorylated Stat1 is required for the regulation of c-Myc, cyclins, and p27Kip1 associated with ATRA-induced G0/G1 arrest of U-937 cells
Blood, July 1, 2003; 102(1): 254 - 261.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
M. Benekli, M. R. Baer, H. Baumann, and M. Wetzler
Signal transducer and activator of transcription proteins in leukemias
Blood, April 15, 2003; 101(8): 2940 - 2954.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
F. Ravandi, M. Talpaz, and Z. Estrov
Modulation of Cellular Signaling Pathways: Prospects for Targeted Therapy in Hematological Malignancies
Clin. Cancer Res., February 1, 2003; 9(2): 535 - 550.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
D. J. Lindner, X. Ma, J. Hu, S. Karra, and D. V. Kalvakolanu
Thioredoxin Reductase Plays a Critical Role in IFN Retinoid-mediated Tumor-Growth Control in Vivo
Clin. Cancer Res., October 1, 2002; 8(10): 3210 - 3218.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
K. E. Luker, C. M. Pica, R. D. Schreiber, and D. Piwnica-Worms
Overexpression of IRF9 Confers Resistance to Antimicrotubule Agents in Breast Cancer Cells
Cancer Res., September 1, 2001; 61(17): 6540 - 6547.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
X. Ma, S. Karra, W. Guo, D. J. Lindner, J. Hu, J. E. Angell, E. R. Hofmann, S. P. M. Reddy, and D. V. Kalvakolanu
Regulation of Interferon and Retinoic Acid-induced Cell Death Activation through Thioredoxin Reductase
J. Biol. Chem., July 6, 2001; 276(27): 24843 - 24854.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J.-B. Yang, Z.-J. Duan, W. Yao, O. Lee, L. Yang, X.-Y. Yang, X. Sun, C. C. Y. Chang, T.-Y. Chang, and B.-L. Li
Synergistic Transcriptional Activation of HumanAcyl-coenzyme A: Cholesterol Acyltransterase-1 Gene by Interferon-{gamma} and All-trans-Retinoic Acid THP-1 Cells
J. Biol. Chem., June 15, 2001; 276(24): 20989 - 20998.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Alsayed, S. Uddin, N. Mahmud, F. Lekmine, D. V. Kalvakolanu, S. Minucci, G. Bokoch, and L. C. Platanias
Activation of Rac1 and the p38 Mitogen-activated Protein Kinase Pathway in Response to All-trans-retinoic Acid
J. Biol. Chem., February 9, 2001; 276(6): 4012 - 4019.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. E. Angell, D. J. Lindner, P. S. Shapiro, E. R. Hofmann, and D. V. Kalvakolanu
Identification of GRIM-19, a Novel Cell Death-regulatory Gene Induced by the Interferon-{beta} and Retinoic Acid Combination, Using a Genetic Approach
J. Biol. Chem., October 27, 2000; 275(43): 33416 - 33426.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Dimberg, K. Nilsson, and F. Oberg
Phosphorylation-deficient Stat1 inhibits retinoic acid-induced differentiation and cell cycle arrest in U-937 monoblasts
Blood, October 15, 2000; 96(8): 2870 - 2878.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Weiden, N. Tanaka, Y. Qiao, B. Y. Zhao, Y. Honda, K. Nakata, A. Canova, D. E. Levy, W. N. Rom, and R. Pine
Differentiation of Monocytes to Macrophages Switches the Mycobacterium tuberculosis Effect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein {beta} Expression
J. Immunol., August 15, 2000; 165(4): 2028 - 2039.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Y.-H. Chen, D. Lavelle, J. DeSimone, S. Uddin, L. C. Platanias, and M. Hankewych
Growth Inhibition of a Human Myeloma Cell Line by All-trans Retinoic Acid Is Not Mediated Through Downregulation of Interleukin-6 Receptors but Through Upregulation of p21WAF1
Blood, July 1, 1999; 94(1): 251 - 259.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Shang, C. R. Baumrucker, and M. H. Green
c-Myc Is a Major Mediator of the Synergistic Growth Inhibitory Effects of Retinoic Acid and Interferon in Breast Cancer Cells
J. Biol. Chem., November 13, 1998; 273(46): 30608 - 30613.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
L. H. Wong, I. Hatzinisiriou, R. J. Devenish, and S. J. Ralph
IFN-{gamma} Priming Up-Regulates IFN-Stimulated Gene Factor 3 (ISGF3) Components, Augmenting Responsiveness of IFN-Resistant Melanoma Cells to Type I IFNs
J. Immunol., June 1, 1998; 160(11): 5475 - 5484.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. E. Angell, D. J. Lindner, P. S. Shapiro, E. R. Hofmann, and D. V. Kalvakolanu
Identification of GRIM-19, a Novel Cell Death-regulatory Gene Induced by the Interferon-{beta} and Retinoic Acid Combination, Using a Genetic Approach
J. Biol. Chem., October 27, 2000; 275(43): 33416 - 33426.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Alsayed, S. Uddin, N. Mahmud, F. Lekmine, D. V. Kalvakolanu, S. Minucci, G. Bokoch, and L. C. Platanias
Activation of Rac1 and the p38 Mitogen-activated Protein Kinase Pathway in Response to All-trans-retinoic Acid
J. Biol. Chem., February 9, 2001; 276(6): 4012 - 4019.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J.-B. Yang, Z.-J. Duan, W. Yao, O. Lee, L. Yang, X.-Y. Yang, X. Sun, C. C. Y. Chang, T.-Y. Chang, and B.-L. Li
Synergistic Transcriptional Activation of HumanAcyl-coenzyme A: Cholesterol Acyltransterase-1 Gene by Interferon-{gamma} and All-trans-Retinoic Acid THP-1 Cells
J. Biol. Chem., June 15, 2001; 276(24): 20989 - 20998.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
X. Ma, S. Karra, W. Guo, D. J. Lindner, J. Hu, J. E. Angell, E. R. Hofmann, S. P. M. Reddy, and D. V. Kalvakolanu
Regulation of Interferon and Retinoic Acid-induced Cell Death Activation through Thioredoxin Reductase
J. Biol. Chem., July 6, 2001; 276(27): 24843 - 24854.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.