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. 1993 Sep;143(3):937–948.

Microtubule disruption stimulates DNA synthesis in bovine endothelial cells and potentiates cellular response to basic fibroblast growth factor.

L Liaw 1, S M Schwartz 1
PMCID: PMC1887204  PMID: 8362986

Abstract

Cultured endothelial cells characteristically form a monolayer and become quiescent at saturation density. This study shows that microtubule destabilization in confluent cultures of bovine aortic endothelial cells stimulates fibroblast growth factor 2 (FGF-2, bFGF)-dependent DNA synthesis. Twenty-four hours after addition of the microtubule-disrupting drug colchicine, tritiated thymidine incorporation increases up to fivefold when compared to control cultures. Significant stimulation is seen with doses from 0.05 to 1.0 microgram/ml. The effect of colchicine is quantitatively similar to stimulation of the same cultures with 5 ng/ml FGF-2. Furthermore, the stimulation of DNA synthesis by colchicine can be completely blocked by the addition of a neutralizing antibody to FGF-2. This suggests that colchicine may stimulate bovine aortic endothelial cells by modulating endogenous FGF-2/receptor interactions or that colchicine acts by a different mechanism that requires the growth factor for mitogenicity. The combined effects of colchicine and FGF-2 are more than additive, which supports the idea that microtubule disruption may facilitate cellular response to FGF-2. Cytochalasin B, preventing actin polymerization, inhibits the mitogenic response to FGF-2 but not the response to colchicine. These results are best interpreted as evidence that colchicine stimulates endothelial cell DNA synthesis by a pathway that requires endogenous FGF-2 and may be facilitating cellular responsiveness to the growth factor by disrupting the monolayer via the cytoskeleton.

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Selected References

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