PT  - JOURNAL ARTICLE
AU  - Elizabeth Alli
AU  - Jin-Ming Yang
AU  - James M. Ford
AU  - William N. Hait
TI  - Reversal of Stathmin-Mediated Resistance to Paclitaxel and Vinblastine in Human Breast Carcinoma Cells
AID  - 10.1124/mol.106.029702
DP  - 2007 May 01
TA  - Molecular Pharmacology
PG  - 1233--1240
VI  - 71
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/71/5/1233.short
4100  - http://molpharm.aspetjournals.org/content/71/5/1233.full
SO  - Mol Pharmacol2007 May 01; 71
AB  - Antimicrotubule agents are commonly used chemotherapy drugs for the treatment of breast and other cancers. However, these agents have variable activity partly because of microtubule regulatory proteins. Stathmin, an 18-kDa phosphoprotein that promotes microtubule depolymerization, was found to be frequently overexpressed in breast cancer. We previously identified stathmin-mediated mechanisms of resistance to antimicrotubule agents, including altered drug binding and delayed transit from G2 into M phase, where these agents are effective in disrupting microtubule dynamics. We hypothesized that by reversing stathmin-mediated depolymerization of microtubules or by promoting entry into mitosis, this could increase sensitivity to antimicrotubule agents in human breast cancer cells overexpressing stathmin. We found that targeting stathmin or wee-1 expression with RNA interference can induce microtubule polymerization and promote G2/M progression, respectively, and sensitize stathmin-overexpressing breast cancer cells to paclitaxel and vinblastine. Furthermore, targeting wee-1 led to the phosphorylation of stathmin, which is known to attenuate its activity. Therefore, these data suggest a novel approach to improving the efficacy of certain antimicrotubule agents against breast cancer by regulating the function of stathmin. The American Society for Pharmacology and Experimental Therapeutics