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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1833-1840. Prepublished online as a Blood First Edition Paper on June 8, 2004; DOI 10.1182/blood-2003-10-3577. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3577v1 104/6/1833    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 Shetzline, S. E. Articles by Gewirtz, A. M. Search for Related Content PubMed PubMed Citation Articles by Shetzline, S. E. Articles by Gewirtz, A. M. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias Susan E. Shetzline, Ravikumar Rallapalli, Kelley J. Dowd, Shaomin Zou, Yuji Nakata, Cezary R. Swider, Anna Kalota, John K. Choi, and Alan M. Gewirtz From the Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia; and the Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA. The c-myb proto-oncogene has been implicated in leukemogenesis, but possible mechanisms remain ill defined. To gain further insight to this process, we used transcript profiling in K562 cells expressing a dominant-negative Myb (MERT) protein. A total of 105 potential Myb gene targets were identified. Neuromedin U (NmU), a peptide affecting calcium transport, underwent the greatest expression change ( 5-fold decrease). To verify a linkage between c-myb and NmU, their mRNA levels were quantitated using real-time polymerase chain reaction in primary acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), as well as normal hematopoietic cells. We found that c-myb was elevated in AML and ALL samples, but NmU expression was increased only in AML cells. Significantly, only AML cells expressed the cognate receptor of NmU, NMU1R, suggesting the presence of a novel autocrine loop. We examined this possibility in detail. Exogenous NmU "rescued" growth suppression in K562-MERT cells and stimulated the growth of primary AML cells. Short interfering RNA "knockdown" of NmU in K562 cells arrested cell growth. Exposing Indo-1–labeled K562 cells to NmU induced an intracellular Ca++ flux consistent with engagement of the NMU1R. Combined, these results suggest that NmU expression is related to Myb and that the NmU/NMU1R axis constitutes a previously unknown growth-promoting autocrine loop in myeloid leukemia cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Saether, T. Berge, M. Ledsaak, V. Matre, A. H. Alm-Kristiansen, O. Dahle, F. Aubry, and O. S. Gabrielsen The Chromatin Remodeling Factor Mi-2{alpha} Acts as a Novel Co-activator for Human c-Myb J. Biol. Chem., May 11, 2007; 282(19): 13994 - 14005. [Abstract] [Full Text] [PDF] Y. Nakata, S. Shetzline, C. Sakashita, A. Kalota, R. Rallapalli, S. I. Rudnick, Y. Zhang, S. G. Emerson, and A. M. Gewirtz c-Myb Contributes to G2/M Cell Cycle Transition in Human Hematopoietic Cells by Direct Regulation of Cyclin B1 Expression Mol. Cell. Biol., March 15, 2007; 27(6): 2048 - 2058. [Abstract] [Full Text] [PDF] K. Takahashi, C. Furukawa, A. Takano, N. Ishikawa, T. Kato, S. Hayama, C. Suzuki, W. Yasui, K. Inai, S. Sone, et al. The Neuromedin U-Growth Hormone Secretagogue Receptor 1b/Neurotensin Receptor 1 Oncogenic Signaling Pathway as a Therapeutic Target for Lung Cancer Cancer Res., October 1, 2006; 66(19): 9408 - 9419. [Abstract] [Full Text] [PDF] A. L. Brown, C. R. Wilkinson, S. R. Waterman, C. H. Kok, D. G. Salerno, S. M. Diakiw, B. Reynolds, H. S. Scott, A. Tsykin, G. F. Glonek, et al. Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling J. Leukoc. Biol., August 1, 2006; 80(2): 433 - 447. [Abstract] [Full Text] [PDF] L. Bullinger and P. J.M. Valk Gene Expression Profiling in Acute Myeloid Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6296 - 6305. [Abstract] [Full Text] [PDF]

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