SEARCH:   Advanced

Blood, 1 September 2005, Vol. 106, No. 5, pp. 1808-1816. Prepublished online as a Blood First Edition Paper on May 12, 2005; DOI 10.1182/blood-2004-12-4832. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4832v1 106/5/1808    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Le Scolan, E. Articles by Moreau-Gachelin, F. Search for Related Content PubMed PubMed Citation Articles by Le Scolan, E. Articles by Moreau-Gachelin, F. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Overexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression Erwan Le Scolan, Dimitri Pchejetski, Yoshiko Banno, Nicole Denis, Patrick Mayeux, William Vainchenker, Thierry Levade, and Françoise Moreau-Gachelin From the Institut National de la Santé et de la Recherche Médicale (Inserm) U528, Institut Curie, Paris, France; Inserm U466, Institut Louis Bugnard, Hôpital Rangueil, Toulouse, France; the Department of Cell Signaling, Gifu University School of Medicine, Gifu, Japan; Inserm, Institut Cochin, Paris, France; and Inserm U362, Institut Gustave Roussy, Villejuif, France. The erythroleukemia developed by spi-1/PU.1-transgenic mice is a model of multistage oncogenic process. Isolation of tumor cells representing discrete stages of leukemic progression enables the dissection of some of the critical events required for malignant transformation. To elucidate the molecular mechanisms of multistage leukemogenesis, we developed a microarray transcriptome analysis of nontumorigenic (HS1) and tumorigenic (HS2) proerythroblasts from spi-1-transgenic mice. The data show that transcriptional up-regulation of the sphingosine kinase gene (SPHK1) is a recurrent event associated with the tumorigenic phenotype of these transgenic proerythroblasts. SPHK1 is an enzyme of the metabolism of sphingolipids, which are essential in several biologic processes, including cell proliferation and apoptosis. HS1 erythroleukemic cells engineered to overexpress the SPHK1 protein exhibited growth proliferative advantage, increased clonogenicity, and resistance to apoptosis in reduced serum level by a mechanism involving activation of the extracellular signal-related kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In addition, SPHK1-overexpressing HS1 cells acquired tumorigenicity when engrafted in vivo. Finally, enforced expression of a dominant-negative mutant of SPHK1 in HS2 tumorigenic cells or treatment with a pharmacologic inhibitor reduced both cell growth and apoptosis resistance. Altogether, these data suggest that overexpression of the sphingosine kinase may represent an oncogenic event during the multistep progression of an erythroleukemia. (Blood. 2005;106:1808-1816) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Kapitonov, J. C. Allegood, C. Mitchell, N. C. Hait, J. A. Almenara, J. K. Adams, R. E. Zipkin, P. Dent, T. Kordula, S. Milstien, et al. Targeting Sphingosine Kinase 1 Inhibits Akt Signaling, Induces Apoptosis, and Suppresses Growth of Human Glioblastoma Cells and Xenografts Cancer Res., September 1, 2009; 69(17): 6915 - 6923. [Abstract] [Full Text] [PDF] W. Li, C.-P. Yu, J.-t. Xia, L. Zhang, G.-X. Weng, H.-q. Zheng, Q.-l. Kong, L.-j. Hu, M.-S. Zeng, Y.-x. Zeng, et al. Sphingosine Kinase 1 Is Associated with Gastric Cancer Progression and Poor Survival of Patients Clin. Cancer Res., February 15, 2009; 15(4): 1393 - 1399. [Abstract] [Full Text] [PDF] J. Li, H.-Y. Guan, L.-Y. Gong, L.-B. Song, N. Zhang, J. Wu, J. Yuan, Y.-J. Zheng, Z.-S. Huang, and M. Li Clinical Significance of Sphingosine Kinase-1 Expression in Human Astrocytomas Progression and Overall Patient Survival Clin. Cancer Res., November 1, 2008; 14(21): 6996 - 7003. [Abstract] [Full Text] [PDF] P. Rimmele, O. Kosmider, P. Mayeux, F. Moreau-Gachelin, and C. Guillouf Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation Blood, April 1, 2007; 109(7): 3007 - 3014. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020