This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alli, E. Articles by Hait, W. N. Search for Related Content PubMed PubMed Citation Articles by Alli, E. Articles by Hait, W. N.

Effect of Stathmin on the Sensitivity to Antimicrotubule Drugs in Human Breast Cancer¹

The Cancer Institute of New Jersey, Departments of Medicine and Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, New Jersey 08901

Stathmin is a p53-regulated protein known to influence microtubule dynamics. Because several chemotherapeutic agents used to treat breast cancer alter the dynamic equilibrium of tubulin polymerization, stathmin may play an important role in determining the sensitivity to these drugs. Therefore, we evaluated the effect of stathmin expression on the action of taxanes and Vinca alkaloids using a panel of human breast cancer cell lines. Cell lines harboring mutant p53 expressed high levels of stathmin. Two cell lines with different levels of endogenous stathmin expression and isogenic-paired cell lines transfected to overexpress stathmin were used to determine whether or not stathmin modulated the sensitivity to drugs. Overexpression of stathmin decreased polymerization of microtubules, markedly decreased binding of paclitaxel, and increased binding of vinblastine. Stathmin overexpression decreased sensitivity to paclitaxel and, to a lesser extent, to vinblastine. In contrast, stathmin content had no significant effect on the sensitivity to chemotherapeutic drugs that do not target microtubules. Cell lines overexpressing stathmin were more likely to enter G₂ but less likely to enter mitosis as determined by fluorescence-activated cell sorting and mitotic index. This effect was magnified when stathmin-overexpressing cells were treated with vinblastine as measured by the detection of proteins phosphorylated in early mitosis. These data suggest that the action of antimicrotubule drugs can be affected by stathmin in at least two ways: (a) altered drug binding; and (b) growth arrest at the G₂ to M boundary. Mutant p53 breast cancers exhibiting high levels of stathmin may be resistant to antimicrotubule agents.

This article has been cited by other articles:

				S. P. Newman, P. A. Foster, C. Stengel, J. M. Day, Y. T. Ho, J.-G. Judde, M. Lassalle, G. Prevost, M. P. Leese, B. V.L. Potter, et al. STX140 Is Efficacious In vitro and In vivo in Taxane-Resistant Breast Carcinoma Cells Clin. Cancer Res., January 15, 2008; 14(2): 597 - 606. [Abstract] [Full Text] [PDF]

				Z. Guan, X.-r. Wang, X.-f. Zhu, X.-f. Huang, J. Xu, L.-h. Wang, X.-b. Wan, Z.-j. Long, J.-n. Liu, G.-k. Feng, et al. Aurora-A, a Negative Prognostic Marker, Increases Migration and Decreases Radiosensitivity in Cancer Cells Cancer Res., November 1, 2007; 67(21): 10436 - 10444. [Abstract] [Full Text] [PDF]

				K. M.R. Bhat and V. Setaluri Microtubule-Associated Proteins as Targets in Cancer Chemotherapy Clin. Cancer Res., May 15, 2007; 13(10): 2849 - 2854. [Abstract] [Full Text] [PDF]

				L. H. Saal, P. Johansson, K. Holm, S. K. Gruvberger-Saal, Q.-B. She, M. Maurer, S. Koujak, A. A. Ferrando, P. Malmstrom, L. Memeo, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity PNAS, May 1, 2007; 104(18): 7564 - 7569. [Abstract] [Full Text] [PDF]

				E. Alli, J.-M. Yang, J. M. Ford, and W. N. Hait Reversal of Stathmin-Mediated Resistance to Paclitaxel and Vinblastine in Human Breast Carcinoma Cells Mol. Pharmacol., May 1, 2007; 71(5): 1233 - 1240. [Abstract] [Full Text] [PDF]

				N. Muthukumaran, K. E. Miletti-Gonzalez, A. K. Ravindranath, and L. Rodriguez-Rodriguez Tumor Necrosis Factor-{alpha} Differentially Modulates CD44 Expression in Ovarian Cancer Cells Mol. Cancer Res., August 1, 2006; 4(8): 511 - 520. [Abstract] [Full Text] [PDF]

				M. H. Soltani, R. Pichardo, Z. Song, N. Sangha, F. Camacho, K. Satyamoorthy, O. P. Sangueza, and V. Setaluri Microtubule-Associated Protein 2, a Marker of Neuronal Differentiation, Induces Mitotic Defects, Inhibits Growth of Melanoma Cells, and Predicts Metastatic Potential of Cutaneous Melanoma Am. J. Pathol., June 1, 2005; 166(6): 1841 - 1850. [Abstract] [Full Text] [PDF]

				S. Honore, K. Kamath, D. Braguer, S. B. Horwitz, L. Wilson, C. Briand, and M. A. Jordan Synergistic Suppression of Microtubule Dynamics by Discodermolide and Paclitaxel in Non-Small Cell Lung Carcinoma Cells Cancer Res., July 15, 2004; 64(14): 4957 - 4964. [Abstract] [Full Text] [PDF]