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This Article Full Text Full Text (PDF) 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 Heberlein, C. Articles by Ostertag, W. Search for Related Content PubMed PubMed Citation Articles by Heberlein, C. Articles by Ostertag, W. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 2 (January 15), 1999: pp. 554-563 Downregulation of c-kit (Stem Cell Factor Receptor) in Transformed Hematopoietic Precursor Cells by Stroma Cells Christoph Heberlein, Jutta Friel, Christine Laker, Dorothee von Laer, Ulla Bergholz, Martina Bögel, Leonie K. Ashman, Karl Klingler, and Wolfram Ostertag From the Department of Cell and Virus Genetics, Heinrich-Pette-Institut für experimentelle Virologie und Immunologie an der Universität Hamburg, Hamburg, Germany; the Division of Haematology, Hanson Centre for Cancer Research, Adelaide, South Australia; and the Institut für Klinische Chemie, Universität zu Köln, Köln, Germany. We show a dramatic downregulation of the stem cell factor (SCF) receptor in different hematopoietic cell lines by murine stroma. Growth of the human erythroid/macrophage progenitor cell line TF-1 is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). However, TF-1 cells clone and proliferate equally well on stroma. Independent stroma-dependent TF-1 clones (TF-1S) were generated on MS-5 stroma. Growth of TF-1S and TF-1 cells on stroma still requires interaction between c-kit (SCF receptor) and its ligand SCF, because antibodies against c-kit inhibit growth to less than 2%. Surprisingly, c-kit receptor expression (RNA and protein) was downregulated by 2 to 3 orders of magnitude in TF-1S and TF-1 cells grown on stroma. This stroma-dependent regulation of the kit receptor in TF-1 was also observed on exposure to kit ligand-negative stroma, thus indicating the need for heterologous receptor ligand interaction. Removal of stroma induced upregulation by 2 to 4 orders of magnitude. Downregulation and upregulation of c-kit expression could also be shown for the megakaryocytic progenitor cell line M-07e and was comparable to that of TF-1, indicating that stroma-dependent regulation of c-kit is a general mechanism. Downregulation may be an economic way to compensate for the increased sensitivity of the c-kit/ligand interaction on stroma. The stroma-dependent c-kit regulation most likely occurs at the transcriptional level, because mechanisms, such as splicing, attenuation, differential promoter usage, or mRNA stability, could be excluded. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Miletic, M. Bruns, K. Tsiakas, B. Vogt, R. Rezai, C. Baum, K. Kühlke, F.-L. Cosset, W. Ostertag, H. Lother, et al. Retroviral Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus J. Virol., July 1, 1999; 73(7): 6114 - 6116. [Abstract] [Full Text]

	Copyright © 1999 by American Society of Hematology         Online ISSN: 1528-0020