Cancer Research Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine  Joint Metastasis Research Society-AACR Conference on Metastasis
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[Cancer Research 62, 2462-2467, May 1, 2002]
© 2002 American Association for Cancer Research


Advances in Brief

Regulation of Microtubule Stability and Mitotic Progression by Survivin1

Alessandra Giodini2, Marko J. Kallio2, Nathan R. Wall, Gary J. Gorbsky, Simona Tognin, Pier Carlo Marchisio, Marc Symons2 and Dario C. Altieri2,,3

Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536 [A. G., N. R. W., D. C. A.]; University of Oklahoma Health Sciences Center, Biomedical Research Center, Oklahoma City, Oklahoma 73104 [M. J. K., G. J. G.]; Vita-Salute University School of Medicine, San Raffaele Scientific Institute, Milano 20132, Italy [S. T., P. C. M.]; and Center for Oncology and Cell Biology, North Shore-Long Island Jewish Research Institute, Manhasset, New York 11030 [M. S.]

Survivin is a member of the inhibitor of apoptosis (IAP) gene family, which has been implicatedin both preservation of cell viability and regulation of mitosis in cancercells. Here, we show that HeLa cells microinjected with a polyclonal antibody to survivin exhibited delayed progression in prometaphase (31.5 ± 6.9 min) and metaphase (126.8 ± 73.8 min), as compared with control injected cells (prometaphase, 21.5 ± 3.3 min; metaphase, 18.9 ± 4.5 min; P < 0.01). Cells injected with the antibody to survivin displayed short mitotic spindles severely depleted of microtubules and occasionally underwent apoptosis without exiting the mitotic block or thereafter. Forced expression of survivin in HeLa cells profoundly influenced microtubule dynamics with reduction of pole-to-pole distance at metaphase (8.57 ± 0.21 µm versus 10.58 ± 0.19 µm; P < 0.0001) and stabilization of microtubules against nocodazole-induced depolymerization in vivo. These data demonstrate that survivin functions at cell division to control microtubule stability and assembly of a normal mitotic spindle. This pathway may facilitate checkpoint evasion and promote resistance to chemotherapy in cancer.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2002 by the American Association for Cancer Research.