Inhibitory Effect of Taxol, a Microtubule Stabilizing Agent, on Induction of DNA Synthesis is Dependent upon Cell Lines and Growth Factors

Cell Structure and Function

Toshinori Ide¹  Kazue Tsuji¹  Akemi Ueno¹ 

[1] Department of Cellular and Molecular Biology, Hiroshima University School of Medicine

关键词: taxol;    microtubules;    DNA synthesis;    growth induction;   

DOI  :  10.1247/csf.17.139

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(24)Cited-By(5)Growth-arrested rat fibroblasts, 3Y1, and human diploid fibroblasts, TIG-1, were induced to synthesize DNA by stimulation with various agents such as fetal bovine serum (FBS), epidermal growth factor (EGF), colcemid, or colchicine. Taxol, a microtubule-stabilizing agent, blocked the induction of DNA synthesis after stimulation with colcemid or colchicine in both cell lines. Taxol inhibited the induction of DNA synthesis after stimulation with FBS or EGF in TIG-1, but did not in 3Y1.12-0-tetradecanoylphorbol-13-acetate (TPA) induced DNA synthesis in TIG-1, which was reduced only partly by taxol. Taxol stabilized or polymerized microtubules in both cell lines. These results indicate that the inhibitory effect of taxol on the induction of DNA syn-thesis varied among cell lines and among growth factors, and suggest that signal transduction processes may be differentiated by taxol sensitivity. In TIG-1 cells, when taxol was added within 6 h, about halfway into the initiation of DNA synthesis after the addition of FBS or EGF, the inhibition of DNA synthesis still occurred. Taxol did not inhibit the induction of c-fos and c-myc genes by FBS or EGF stimulation. Colchicine itself did not in-duce these genes in TIG-1. Thus, taxol appeared to inhibit the induction of DNA synthesis not by blockage in the early transduction process of the growth signal from the cell surface to nuclei but by blockage in processes operating in the mid- or late-prereplicative phase.

【 授权许可】

Unknown