Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells

Elizabeth Alli, Jin Ming Yang, James M. Ford, William N. Hait

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1233-1240
Number of pages8
JournalMolecular pharmacology
Volume71
Issue number5
DOIs
StatePublished - May 1 2007

Fingerprint

Stathmin
Vinblastine
Paclitaxel
Breast Neoplasms
Microtubules
Microtubule Proteins
Phosphoproteins
RNA Interference
Mitosis
Polymerization
Pharmaceutical Preparations
Cell Division
Phosphorylation
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Alli, Elizabeth ; Yang, Jin Ming ; Ford, James M. ; Hait, William N. / Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. In: Molecular pharmacology. 2007 ; Vol. 71, No. 5. pp. 1233-1240.
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Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. / Alli, Elizabeth; Yang, Jin Ming; Ford, James M.; Hait, William N.

In: Molecular pharmacology, Vol. 71, No. 5, 01.05.2007, p. 1233-1240.

Research output: Contribution to journalArticle

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