Abstract
Tubulin, the main component of microtubules, is a major target for antitumor drugs such as vinblastine. We have recently discovered that the βII isotype of tubulin is present in the nuclei of cultured rat kidney mesangial cells, smooth-muscle-like cells present in the renal glomerular mesangium (Walss C, Kreisberg JI, Ludueña RF: Cell Motil Cytoskeleton 42: 274–284, 1999). Here, we have investigated the effect of vinblastine on nuclear βII-tubulin in these cells. We have found that, at concentrations of 15 nM and higher, vinblastine caused a reversible loss of βII-tubulin from the nucleus. Our results raise the possibility that nuclear βII-tubulin constitutes a population of tubulin that could be a novel target for antitumor drugs such as vinblastine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dustin P (ed.): Microtubules, 2nd edn. Springer-Verlag, Berlin, 1984
Wilson L, Jordan MA: Pharmacological probes of microtubule function. In: Hyams JS, Lloyd CW (eds) Microtubules. Wiley-Liss, New York, 1994, pp 59–83
Gerzon K: Dimeric catharanthus alkaloids. In: Cassady JM, Douros JD (eds), Anticancer Agents Based on Natural Product Models. Academic Press, New York, 1980, pp 271–317
Owellen RJ, Hartke CA, Dickerson RM, Haines FO: Inhibition of tubulin microtubule polymerization by drugs of the Vinca alkaloid class. Cancer Res 36: 3798–3802, 1976
Na GC, Timasheff SN: In vitro vinblastine-induced tubulin paracrystals. J Biol Chem 257: 10387–10391, 1982
Jordan MA, Thrower D, Wilson L: Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51: 2212–2222, 1991
Walss C, Kreisberg JI, Ludueña RF: Presence of the β II isotype of tubulin in the nuclei of cultured mesangial cells from rat kidney. Cell Motil Cytoskeleton 42: 274–284, 1999
Walss-Bass C, Xu K, David S, Fellous A, Ludueña RF: Occurrence of nuclear β II-tubulin in cultured cells. Cell Tiss Res 2002 (in press).
Tsukidate K, Yamamoto K, Snyder JW, Farber JL: Microtubule antagonists activate programmed cell death (apoptosis) in cultured rat hepatocytes. Am J Pathol 143: 918–925, 1993
Ausiello DA, Kreisberg JI, Roy C, Karnovsky MJ: Contraction of cultured cells of apparent mesangial origin after stimulation with angiotensin II and arginine vasopressin. J Clin Invest 65: 754–760, 1980
Kreisberg JI, Venkatachalam MA, Patel PY: Cyclic AMP-associated shape change and its reversal by PGE2. Kidney Int 25: 874–879, 1984
Kreisberg JI, Venkatachalam MA: Vasoactive agents affect mesangial cell adhesion. Am J Physiol 251: C505–C511, 1986
Banerjee A, Roach MC, Wall KA, Lopata MA, Cleveland DW, Ludueña RF: A monoclonal antibody against the type II isotype of β-tubulin. Preparation of isotypically altered tubulin. J Biol Chem 263: 3029–3034, 1988
Roach MC, Boucher VL, Walss C, Ravdin P, Ludueña RF: Preparation of a monoclonal antibody specific for the class I isotype of β-tubulin: the β isotypes of tubulin differ in their cellular distributions within human tissues. Cell Motil Cytoskeleton 39: 273–285, 1998
Khan IA, Ludueña RF: Effect of vinblastine on the assembly of isotypically pure tubulins from bovine brain. Mol Biol Cell 6: 30a, 1995
Xu K, Ludueña RF: Characterization of nuclear β II-tubulin in tumor cells: a possible novel target for taxol. Cell Motil Cytoskeleton, 2002 (in press)
Jordan MA, Wendell K, Gardiner D, Derry WB, Copp H, Wilson L: Mitotic block induced in HeLa cells by low concentrations of paclitaxel (taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 56: 816–825, 1996
Sorger PK, Dobles M, Tournebize R, Hyman AA: Coupling cell division and cell death to microtubule dynamics. Curr Opin Cell Biol 9: 807–814, 1997
Walss-Bass C, Kreisberg JI, Ludueña RF: Mechanism of localization of β II-tubulin in the nuclei of cultured rat kidney mesangial cells. Cell Motil Cytoskeleton 49: 208–217, 2001
Floege J, Topley N, Hoppe J, Barrett TB, Resch K: Mitogenic effect of platelet-derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines. Clin Exp Immunol 86: 334–341, 1991
Creasey WA: Modifications in biochemical pathways produced by the Vinca alkaloids. Cancer Chemother Res 52: 501–507, 1968
Bernstam VA, Gray RH, Bernstein IA: Effect of microtubule-disrupting drugs on protein and RNA synthesis in Physarum polycephalum Amoebae. Arch Microbiol 128: 34–40, 1980
Jordan MA, Toso RJ, Thrower D, Wilson L: Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Nat Acad Sci USA 90: 9552–9556, 1993
Derry WB, Wilson L, Jordan MA: Low potency of taxol at microtubule minus ends: implications for its antimitotic and therapeutic mechanism. Cancer Res 58: 1177–1184, 1998
Yvon AM, Wadsworth P, Jordan MA: Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol Biol Cell 10: 947–959, 1999
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Walss-Bass, C., Kreisberg, J.I. & Ludueña, R.F. Effect of the Antitumor Drug Vinblastine on Nuclear βII-tubulin in Cultured Rat Kidney Mesangial Cells. Invest New Drugs 21, 15–20 (2003). https://doi.org/10.1023/A:1022947706151
Issue Date:
DOI: https://doi.org/10.1023/A:1022947706151