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Journal of Cell Science, Vol 112, Issue 13 2213-2221, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
K Blade, DR Menick and F Cabral
Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
Recent studies have suggested a correlation between increased expression of specific beta-tubulin isotypes and paclitaxel resistance in drug-selected cell lines. In an attempt to establish a causal link, we have transfected Chinese hamster ovary cells with cDNAs encoding epitope-tagged class I, II, and IVb beta-tubulins, as well as a class I beta-tubulin with a mutation previously characterized in a paclitaxel resistant mutant. To eliminate possible toxicity that might be associated with overexpression of non-native tubulin, each of the cDNAs was placed under the control of a tetracycline regulated promoter. All transfected cDNAs produced assembly competent tubulin whose synthesis could be turned off or on by the presence or absence of tetracycline. Production of betaI, betaII, or betaIVb tubulin had no effect on the sensitivity of the cells to paclitaxel, but production of the mutant betaI-tubulin conferred clear resistance to the drug. We conclude from these experiments that simple overexpression of class I, II, or IVb isoforms of beta-tubulin is insufficient to confer resistance to paclitaxel.
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  G. Cheng, M. R. Zile, M. Takahashi, C. F. Baicu, D. D. Bonnema, F. Cabral, D. R. Menick, and G. Cooper 4th A direct test of the hypothesis that increased microtubule network density contributes to contractile dysfunction of the hypertrophied heart Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2231 - H2241. [Abstract] [Full Text] [PDF]
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 H. Yang and F. Cabral Heightened Sensitivity to Paclitaxel in Class IVa beta-Tubulin-transfected Cells Is Lost as Expression Increases J. Biol. Chem., September 14, 2007; 282(37): 27058 - 27066. [Abstract] [Full Text] [PDF]
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M. Hari, F. Loganzo, T. Annable, X. Tan, S. Musto, D. B. Morilla, J. H. Nettles, J. P. Snyder, and L. M. Greenberger Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of {beta}-tubulin (Asp26Glu) and less stable microtubules. Mol. Cancer Ther., February 1, 2006; 5(2): 270 - 278. [Abstract] [Full Text] [PDF]
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 R. E. Ferguson, C. Taylor, A. Stanley, E. Butler, A. Joyce, P. Harnden, P. M. Patel, P. J. Selby, and R. E. Banks Resistance to the Tubulin-Binding Agents in Renal Cell Carcinoma: No Mutations in the Class I {beta}-Tubulin Gene but Changes in Tubulin Isotype Protein Expression Clin. Cancer Res., May 1, 2005; 11(9): 3439 - 3445. [Abstract] [Full Text] [PDF]
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S. Don, N. M. Verrills, T. Y.E. Liaw, M. L.M. Liu, M. D. Norris, M. Haber, and M. Kavallaris Neuronal-associated microtubule proteins class III {beta}-tubulin and MAP2c in neuroblastoma: Role in resistance to microtubule-targeted drugs Mol. Cancer Ther., September 1, 2004; 3(9): 1137 - 1146. [Abstract] [Full Text] [PDF]
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 C. D. Katsetos, A. Legido, E. Perentes, and S. J. Mork Class III {beta}-Tubulin Isotype: A Key Cytoskeletal Protein at the Crossroads of Developmental Neurobiology and Tumor Neuropathology J Child Neurol, December 1, 2003; 18(12): 851 - 866. [Abstract] [PDF]
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M. Hari, Y. Wang, S. Veeraraghavan, and F. Cabral Mutations in {alpha}- and {beta}-Tubulin That Stabilize Microtubules and Confer Resistance to Colcemid and Vinblastine Mol. Cancer Ther., July 1, 2002; 2(7): 597 - 605. [Abstract] [Full Text] [PDF]
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 S. B. Barlow, M. L. Gonzalez-Garay, and F. Cabral Paclitaxel-dependent mutants have severely reduced microtubule assembly and reduced tubulin synthesis J. Cell Sci., January 9, 2002; 115(17): 3469 - 3478. [Abstract] [Full Text] [PDF]
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 M. Kavallaris, A. S. Tait, B. J. Walsh, L. He, S. B. Horwitz, M. D. Norris, and M. Haber Multiple Microtubule Alterations Are Associated with Vinca Alkaloid Resistance in Human Leukemia Cells Cancer Res., August 1, 2001; 61(15): 5803 - 5809. [Abstract] [Full Text] [PDF]
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 P. Duesberg, R. Stindl, and R. Hehlmann Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy PNAS, December 19, 2000; 97(26): 14295 - 14300. [Abstract] [Full Text] [PDF]
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R. B. Montgomery, J. Guzman, D. M. O'Rourke, and W. L. Stahl Expression of Oncogenic Epidermal Growth Factor Receptor Family Kinases Induces Paclitaxel Resistance and Alters beta -Tubulin Isotype Expression J. Biol. Chem., June 2, 2000; 275(23): 17358 - 17363. [Abstract] [Full Text] [PDF]
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