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Blood, 1 July 2004, Vol. 104, No. 1, pp. 237-242. Prepublished online as a Blood First Edition Paper on March 16, 2004; DOI 10.1182/blood-2003-07-2203. This Article Full Text (PDF) All Versions of this Article: 2003-07-2203v1 104/1/237    most recent Alert me when this article is cited Alert me if a correction is posted 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 Ikezoe, T. Articles by Koeffler, H P Search for Related Content PubMed PubMed Citation Articles by Ikezoe, T. Articles by Koeffler, H P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 2, 2003 Accepted February 17, 2004 Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Antagonizes the Effects of Retinoids in Myeloid Leukemia Cells Takayuki Ikezoe*, Sakae Tanosaki, Utz Krug, Bingrong Liu, Pinchas Cohen, Hirokuni Taguchi, and H P Koeffler Internal Medicine, Kochi Medical School, Nankoku, Kochi, Japan; Hematology/Oncology, Cedars-Sinai Research Institute, Los Angeles, CA, USA Hematology/Oncology, Cedars-Sinai Research Institute, Los Angeles, CA, USA Pediatric Endocrinology, UCLA, Los Angeles, CA, USA Internal Medicine, Kochi Medical School, Nankoku, Kochi, Japan * Corresponding author; email: ikezoet{at}med.kochi-ms.ac.jp. Insulin-like growth factor binding protein-3 (IGFBP-3) can cause both growth suppressive and pro-apoptotic effects of retinoids in many types of cancer cells. However, the expression and effects of IGFBP-3 in myeloid leukemia cells has not been elucidated. In this study, we found no IGFBP-3 expression in the human myeloid leukemia cell lines either at baseline or after stimulation with all-trans retinoic acid (ATRA). Human recombinant IGFBP-3 induced growth arrest and apoptosis of HL-60 and NB4 cells. We have previously identified RXR as a nuclear receptor for IGFBP-3 and proceeded to examine further the role of this interaction in leukemia cell lines. In signaling assays, IGFBP-3 potently suppressed RAR- and VDR-mediated signaling, while enhancing RXR signaling. Interestingly, when IGFBP-3 was administered to these cells in combination with a RAR selective ligand, the ability of these retinoids to induce differentiation was blunted. On the other hand, IGFBP-3 enhanced the effect of a RXR selective ligand to induce differentiation of HL-60 and NB4 cells. Further studies showed that IGFBP-3 down-regulated (at the transcriptional level) the retinoid-induced expression of C/EBP in NB4 cells. Taken together, IGFBP-3 possesses anti-proliferative activity against myeloid leukemia cells; while it enhances signaling through RXR/RXR, it blunts signaling by activated RAR/RXR. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Zappala, C. Elbi, J. Edwards, J. Gorenstein, M. M. Rechler, and N. Bhattacharyya Induction of Apoptosis in Human Prostate Cancer Cells by Insulin-Like Growth Factor Binding Protein-3 Does Not Require Binding to Retinoid X Receptor-{alpha} Endocrinology, April 1, 2008; 149(4): 1802 - 1812. [Abstract] [Full Text] [PDF] L. J. Schedlich, A. Muthukaruppan, M. K. O'Han, and R. C. Baxter Insulin-Like Growth Factor Binding Protein-5 Interacts with the Vitamin D Receptor and Modulates the Vitamin D Response in Osteoblasts Mol. 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Cancer Ther., June 1, 2007; 6(6): 1851 - 1857. [Abstract] [Full Text] [PDF] R. H. Muzumdar, X. Ma, S. Fishman, X. Yang, G. Atzmon, P. Vuguin, F. H. Einstein, D. Hwang, P. Cohen, and N. Barzilai Central and Opposing Effects of IGF-I and IGF-Binding Protein-3 on Systemic Insulin Action. Diabetes, October 1, 2006; 55(10): 2788 - 2796. [Abstract] [Full Text] [PDF] K.-W. Lee, L. Ma, X. Yan, B. Liu, X.-k. Zhang, and P. Cohen Rapid Apoptosis Induction by IGFBP-3 Involves an Insulin-like Growth Factor-independent Nucleomitochondrial Translocation of RXR{alpha}/Nur77 J. Biol. Chem., April 29, 2005; 280(17): 16942 - 16948. [Abstract] [Full Text] [PDF]

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