Taxol Induces the Hematopoietic Growth Factor Granulocyte-Macrophage Colony-stimulating Factor in Murine B-Cells by Stabilization of Granulocyte-Macrophage Colony-stimulating Factor Nuclear RNA

作者: Dov H. Pluznik , Tomohiro Sawada , Nancy S. Lee

DOI:

关键词: Cytotoxic T cellCytokineInternal medicineMessenger RNAInterleukin 4Cell biologyGranulocyte macrophage colony-stimulating factorBiologyEndocrinologyGrowth factorHematopoietic growth factorCell culture

摘要: Taxol, a microtubule-stabilizing agent, has been shown to have anti-neoplastic activity against various tumors. In addition, it that taxol resembles bacterial lipopolysaccharide in its ability activate macrophages. Recently we induces the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) murine B-cell lines. light similarity and their effects on macrophages, tested whether could also induce GM-CSF present study used B-lymphoma cell line M12.4.1. unstimulated cells, no mRNA was detected, whereas taxol-stimulated cells at concentration 30 µm, induced 4–8 h after stimulation. This induction down-regulated by 10 ng/ml interleukin 4. Actinomycin D chase experiments revealed 4 did not affect half-life taxol-induced cytoplasmic mRNA, nor alter gene transcription. Polymerase chain reaction analysis nuclear RNA, utilizing probes specific for sequences first intron GM-CSF, indicated enhances accumulation precursor RNA decreases this accumulation. The shows novel inducing release hematopoietic growth from B-cells. Since is known recruit macrophages enhance cytotoxicity tumor our observations suggest part antitumor may be due synergistic together with direct cytotoxic actions through microtubule stabilization.

参考文章(19)
Rowinsky Ek, Clinical pharmacology of Taxol. Journal of The National Cancer Institute Monographs. pp. 25- 37 ,(1993)
N.M. Gough, D. Metcalf, J. Gough, D. Grail, A.R. Dunn, Structure and expression of the mRNA for murine granulocyte-macrophage colony stimulating factor. The EMBO Journal. ,vol. 4, pp. 645- 653 ,(1985) , 10.1002/J.1460-2075.1985.TB03678.X
R. B. Cohen, T. R. Boal, B. Safer, Increased eIF-2 alpha expression in mitogen-activated primary T lymphocytes. The EMBO Journal. ,vol. 9, pp. 3831- 3837 ,(1990) , 10.1002/J.1460-2075.1990.TB07601.X
S N Vogel, C L Manthey, P Y Perera, M E Brandes, Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages. Journal of Immunology. ,vol. 149, pp. 2459- 2465 ,(1992)
C Kanellopoulos-Langevin, R Asofsky, D H Sachs, R M Merwin, K J Kim, Establishment and Characterization of BALB/c Lymphoma Lines with B Cell Properties Journal of Immunology. ,vol. 122, pp. 549- 554 ,(1979)
A H Ding, E Sanchez, S Srimal, C F Nathan, Macrophages rapidly internalize their tumor necrosis factor receptors in response to bacterial lipopolysaccharide. Journal of Biological Chemistry. ,vol. 264, pp. 3924- 3929 ,(1989) , 10.1016/S0021-9258(19)84941-4
David S. Ettinger, Philip J. Burke, Robert W. Tucker, Ross C. Donehower, Eric K. Rowinsky, Judith E. Karp, Phase I and pharmacodynamic study of taxol in refractory acute leukemias. Cancer Research. ,vol. 49, pp. 4640- 4647 ,(1989)
Andrew P. Feinberg, Bert Vogelstein, A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity Analytical Biochemistry. ,vol. 132, pp. 6- 13 ,(1983) , 10.1016/0003-2697(83)90418-9