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Cell Growth & Differentiation, Vol 5, Issue 4 367-372, Copyright © 1994 by American Association of Cancer Research


ARTICLES

Raf-1 is a necessary component of the mitogenic response of the human megakaryoblastic leukemia cell line MO7 to human stem cell factor, granulocyte-macrophage colony-stimulating factor, interleukin 3, and interleukin 9

U Brennscheidt, D Riedel, W Kolch, R Bonifer, MA Brach, A Ahlers, RH Mertelsmann and F Herrmann
Department of Medical Oncology and Applied Molecular Biology, Free University of Berlin, Germany.

We have examined the role of Raf-1 in the mitogenic response of the factor-deprived human megakaryoblastic leukemia cell line MO7 to recombinant human granulocyte-macrophage colony-stimulating factor, interleukin 3, interleukin 9, and stem cell factor by using c-raf antisense oligodeoxyribonucleotides. Uptake of oligodeoxyribonucleotides by MO7 cells was maximal at 5-10 h in culture, and oligomers remained stable in these cells for at least 24 h. Treatment of MO7 cells with the antisense oligomer resulted in intracellular oligomer/mRNA duplex formation followed by efficient translation blockade of c-raf-1. In contrast, sense and non-sense oligodeoxyribonucleotides failed to form intracellular duplexes and did not interfere with translation of c-raf-1, suggesting specific elimination of c-raf-1 by the antisense oligodeoxyribonucleotide. Furthermore, exposure of MO7 cells to c-raf-1 antisense prevented factor-induced nuclear translocation of Raf-1. Most importantly, proliferation of MO7 cells ([3H]thymidine incorporation) enabled by these growth factors was significantly reduced when the c-raf-1 antisense oligodeoxyribonucleotide was added to cultures, whereas the mitogenic response to these factors remained almost unaffected in the presence of sense and non-sense oligodeoxyribonucleotides.


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1994 by the American Association of Cancer Research.