Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint

234Citations
Citations of this article
90Readers
Mendeley users who have this article in their library.

Abstract

Paclitaxel stabilizes microtubules, causing mitotic arrest and activating the spindle assembly checkpoint. We determined whether suppression of the checkpoint genes Mad2 and BubR1 affects paclitaxel resistance and whether overexpression of Mad2 protein in checkpoint-defective cells enhances paclitaxel sensitivity. Suppression of Mad2 and BubR1 in paclitaxel-treated cancer cells abolished checkpoint function, resulting in paclitaxel resistance that correlated with suppression of cyclin-dependent kinase-1 activity. In contrast, overexpression of Mad2 in cells with a checkpoint defect attributable to low Mad2 expression restored checkpoint function, resulting in enhanced paclitaxel sensitivity that correlated with enhanced cyclin-dependent kinase-1 activity. However, overexpression of Mad2 failed to enhance paclitaxel sensitivity via checkpoint activation in Mad2-independent checkpoint-defective and -intact cells. Thus, checkpoint function is required for paclitaxel sensitivity. These findings show that any molecules that could interfere with the spindle assembly checkpoint could generate paclitaxel resistance in any patient.

Cite

CITATION STYLE

APA

Sudo, T., Nitta, M., Saya, H., & Ueno, N. T. (2004). Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint. Cancer Research, 64(7), 2502–2508. https://doi.org/10.1158/0008-5472.CAN-03-2013

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free