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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1280-1287. Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-04-1614. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1614v1 105/3/1280    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 Crowder, C. Articles by Rudikoff, S. Search for Related Content PubMed PubMed Citation Articles by Crowder, C. Articles by Rudikoff, S. Related Collections Immunobiology Neoplasia Apoptosis Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA PML mediates IFN-–induced apoptosis in myeloma by regulating TRAIL induction Chun Crowder, Øyvind Dahle, R. Eric Davis, Odd S. Gabrielsen, and Stuart Rudikoff From the Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Molecular Biosciences, University of Oslo, Norway; and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Interferon (IFN) induces expression of proapoptotic genes and has been used in the clinical treatment of multiple myeloma. The promyelocytic leukemia (PML) gene is an IFN-induced target that encodes a tumor suppressor protein. PML protein is typically localized within discrete speckled nuclear structures termed PML nuclear bodies (NBs). Multiple myeloma cells demonstrate differential responses to IFN treatment, the mechanism of which is largely unknown. Herein, we show that growth inhibition effects of IFN- in myeloma cells correlate with PML NBs and tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) induction, whereas known IFN targets including signal transducer and activator of transcription-1 (STAT1), STAT3, p38, and Daxx cannot account for these differential responses. RNAi silencing of PML blocks IFN-–induced apoptosis in myeloma cells and correspondingly down-regulates TRAIL expression. Similarly, stable expression of a dominant negative TRAIL receptor DR5 partially blocks IFN-induced cell death. These results demonstrate that PML and TRAIL play important roles in IFN-induced apoptosis and identify TRAIL as a novel downstream transcriptional target of PML. Identification of PML and PML NBs as effectors of IFN responses provides insights into mechanisms by which tumor cells exhibit resistance to this class of agents and may prove useful in assessing treatment regimens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Chiron, C. Pellat-Deceunynck, M. Amiot, R. Bataille, and G. Jego TLR3 Ligand Induces NF-{kappa}B Activation and Various Fates of Multiple Myeloma Cells Depending on IFN-{alpha} Production J. Immunol., April 1, 2009; 182(7): 4471 - 4478. [Abstract] [Full Text] [PDF] K. Herzer, T. G. Hofmann, A. Teufel, C. C. Schimanski, M. Moehler, S. Kanzler, H. Schulze-Bergkamen, and P. R. Galle IFN-{alpha}-Induced Apoptosis in Hepatocellular Carcinoma Involves Promyelocytic Leukemia Protein and TRAIL Independently of p53 Cancer Res., February 1, 2009; 69(3): 855 - 862. [Abstract] [Full Text] [PDF] T. Peng, J. Zhu, Y. Hwangbo, L. Corey, and R. E. Bumgarner Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts J. Virol., February 15, 2008; 82(4): 1934 - 1945. [Abstract] [Full Text] [PDF] S. Lee, J. Chen, G. Zhou, R. Z. Shi, G. G. Bouffard, M. Kocherginsky, X. Ge, M. Sun, N. Jayathilaka, Y. C. Kim, et al. Gene expression profiles in acute myeloid leukemia with common translocations using SAGE PNAS, January 24, 2006; 103(4): 1030 - 1035. [Abstract] [Full Text] [PDF]

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