antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-101Research ArticleОБЗОРЫREVIEWSБелок микротрубочек βIII-тубулин: строение, экспрессия и функции в нормальных и опухолевых клеткахMicrotubule Protein βIII-Tubulin: Structure, Expression and Functions in Normal and Tumor CellsМамичевИ. А.MamichevI. A.noemail@neicon.ruБогушТ. А.BogushT. A.noemail@neicon.ruБогушЕ. А.BogushE. A.noemail@neicon.ruТерентьеваН. С.TerentyevaN. S.noemail@neicon.ruКирсановВ. Ю.KirsanovV. Y.noemail@neicon.ruДавыдовМ. М.DavydovM. M.noemail@neicon.ruНациональный медицинский исследовательский центр онкологии им. Н. Н. Блохина МЗ РФРоссияN. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederatonRussian FederationМосковский государственный университет им. М. В. ЛомоносоваРоссияM. V. Lomonosov Moscow State UniversityRussian FederationПервый московский государственный медицинский университет им. И. М. СеченоваРоссияI. M. Sechenov First Moscow State Medical UniversityRussian Federation201806052020637-87990Copyright © ООО «Издательство ОКИ», 20202020ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/101

В обзоре литературы представлены данные о белке микротрубочек βIII-тубулине (TUBB3): его структуре, функциях, роли в опухолевой прогрессии, экспрессии в нормальных клетках, а также в опухолях нервной системы и в эпителиальных опухолях разных локализаций. Рассмотрены основные принципы работы системы микротрубочек и связь TUBB3 с родственными белками семейства ß-тубулинов. Проанализированы перспективы использования TUBB3 в клинической практике как прогностического маркера агрессивности течения заболевания и резистентности опухоли к лекарственной терапии. Сформулировано новое представление о молекулярной диагностике локальной распространённости опухолевого процесса на основании сравнительной оценки уровня экспрессии TUBB3 в нормальной и опухолевой ткани каждого больного. В заключение обоснована необходимость изучения экспрессии TUBB3 и других опухолевый маркеров не только в самой опухоли, но и в нормальной ткани органа, визуально не вовлечённой в опухолевый процесс.

The present review contains data on microtubular protein ßIII-tubulin (TUBB3): its structure, functions, role in tumor progression, expression in normal cells and in neural and epithelial tumors of different origins. Basic working principles of microtubular system and links between TUBB3 and related β-tubulins are also briefly reviewed. We analyzed the clinical potential of TUBB3 as prognostic marker of tumor aggressiveness and drug-resistance and suggested that locally disseminated tumor cells might be found by comparison of TUBB3 expression in normal and tumor tissue of each patient. Finally, we conclude that screening for TUBB3 and other tumor markers in morphologically normal tissue adjacent to the tumor is essential for accurate diagnostics.

микротрубочкицитоскелетопухолевая трансформацияметастазированиелекарственная устойчивостьпрогностические маркерымолекулярная диагностика злокачественных новообразованийß-тубулинTUBB3ß-tubulinTUBB3microtubulescytoskeletonneoplastic transformationmetastasisdrug-resistanceprognostic markersmolecular diagnosis of malignant tumorsReferencesJordan M.A., Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4: 253-265.Jordan M.A., Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4: 253-265.David-Pfeuty T., Erickson H.P., Pantaloni D. Guanosinetriphosphatase activity of tubulin associated with microtubule assembly. Proc Natl Acad Sci USA 1977; 74: 12: 5372-5376.David-Pfeuty T., Erickson H.P., Pantaloni D. Guanosinetriphosphatase activity of tubulin associated with microtubule assembly. Proc Natl Acad Sci USA 1977; 74: 12: 5372-5376.Rezania V., Azarenko O., Jordan M.A. et al. Microtubule assembly of isotypically purified tubulin and its mixtures. Biophys J 2008; 95: 4: 1993-2008.Rezania V., Azarenko O., Jordan M.A. et al. Microtubule assembly of isotypically purified tubulin and its mixtures. Biophys J 2008; 95: 4: 1993-2008.Luduena R.F. Multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol 1998; 178: 207-275.Luduena R.F. Multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol 1998; 178: 207-275.Gadadhar S., Bodakuntla S., Natarajan K. et al. The tubulin code at a glance. J Cell Sci 2017; 130: 8: 1347-1353.Gadadhar S., Bodakuntla S., Natarajan K. et al. The tubulin code at a glance. J Cell Sci 2017; 130: 8: 1347-1353.Luduena R.F. A hypothesis on the origin and evolution of tubulin. Int Rev Cell Mol Biol 2013; 302: 41-185.Luduena R.F. A hypothesis on the origin and evolution of tubulin. Int Rev Cell Mol Biol 2013; 302: 41-185.Ono S. Ancient linkage groups and frozen accidents. Nature. 1973; 244: 5414: 259-262.Ono S. Ancient linkage groups and frozen accidents. Nature. 1973; 244: 5414: 259-262.Katsetos C.D., Herman M.M., Mörk S.J. Class III beta-tubulin in human development and cancer. Cell Motil Cytoskeleton 2003; 55: 2: 77-96.Katsetos C.D., Herman M.M., Mörk S.J. Class III beta-tubulin in human development and cancer. Cell Motil Cytoskeleton 2003; 55: 2: 77-96.Panda D., Miller H.P., Banerjee A. et al. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci U. S. A. 1994; 91: 24: 11358-11362.Panda D., Miller H.P., Banerjee A. et al. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci U. S. A. 1994; 91: 24: 11358-11362.Jiang Y.Q., Oblinger M.M. Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. J Cell Sci 1992; 103 ( Pt 3): 643-651.Jiang Y.Q., Oblinger M.M. Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. J Cell Sci 1992; 103 ( Pt 3): 643-651.Drâberovâ E., Del Valle L., Gordon J. et al. Class III β-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. Neuropathol Exp Neurol 2008; 2008: 341-354.Drâberovâ E., Del Valle L., Gordon J. et al. Class III β-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. Neuropathol Exp Neurol 2008; 2008: 341-354.Portyanko A., Kovalev P., Gorgun J., Cherstvoy E. Beta(III)-tubulin at the invasive margin of colorectal cancer: possible link to invasion. Virchows Arch 2009; 454: 5: 541-548.Portyanko A., Kovalev P., Gorgun J., Cherstvoy E. Beta(III)-tubulin at the invasive margin of colorectal cancer: possible link to invasion. Virchows Arch 2009; 454: 5: 541-548.Jouhilahti E.M., Peltonen S., Peltonen J. Class III beta-tubulin is a component of the mitotic spindle in multiple cell types. J Histochem Cytochem 2008; 56: 12: 1113-1119.Jouhilahti E.M., Peltonen S., Peltonen J. Class III beta-tubulin is a component of the mitotic spindle in multiple cell types. J Histochem Cytochem 2008; 56: 12: 1113-1119.Guo J., Walss-Bass C., Luduena R.F. The beta isotypes of tubulin in neuronal differentiation. Cytoskeleton (Hoboken) 2010; 67: 7: 431-441.Guo J., Walss-Bass C., Luduena R.F. The beta isotypes of tubulin in neuronal differentiation. Cytoskeleton (Hoboken) 2010; 67: 7: 431-441.Fanara P. et al. Stabilization of hyperdynamic microtubules is neuroprotective in amyotrophic lateral sclerosis. J Biol Chem 2007; 282: 32: 23465-23472.Fanara P. et al. Stabilization of hyperdynamic microtubules is neuroprotective in amyotrophic lateral sclerosis. J Biol Chem 2007; 282: 32: 23465-23472.Gan P.P., Pasquier E., Kavallaris M. Class III beta-tubulin mediates sensitivity to chemotherapeutic drugs in non small cell lung cancer. Cancer Res 2007; 67: 19: 9356-9363.Gan P.P., Pasquier E., Kavallaris M. Class III beta-tubulin mediates sensitivity to chemotherapeutic drugs in non small cell lung cancer. Cancer Res 2007; 67: 19: 9356-9363.Davies K.J., Doroshow J.H. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem 1986; 261: 7: 3060-3067.Davies K.J., Doroshow J.H. Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase. J Biol Chem 1986; 261: 7: 3060-3067.Sheldon K.L., Maldonado E.N., Lemasters J.J. et al. Phosphorylation of voltage-dependent anion channel by serine/threonine kinases governs its interaction with tubulin. PLoS One / ed. Kahle P J 2011; 6: 10: e25539.Sheldon K.L., Maldonado E.N., Lemasters J.J. et al. Phosphorylation of voltage-dependent anion channel by serine/threonine kinases governs its interaction with tubulin. PLoS One / ed. Kahle P J 2011; 6: 10: e25539.Rostovsteva, T.K., Gurnev, P.A., Chen, M.Y., Bezrukov S.M. Membrane lipid composition regulates tubulin interaction with mitochondrial voltage-dependent anion channel. Biol Chem 2012; 287: 29589-29598.Rostovsteva, T.K., Gurnev, P.A., Chen, M.Y., Bezrukov S.M. Membrane lipid composition regulates tubulin interaction with mitochondrial voltage-dependent anion channel. Biol Chem 2012; 287: 29589-29598.Cicchillitti L., Penci R., Di Michele M. et al. Proteomic characterization of cytoskeletal and mitochondrial class III beta-tubulin. Mol Cancer Ther 2008; 7: 7: 2070-2079.Cicchillitti L., Penci R., Di Michele M. et al. Proteomic characterization of cytoskeletal and mitochondrial class III beta-tubulin. Mol Cancer Ther 2008; 7: 7: 2070-2079.McCarroll J.A., Gan P.P., Erlich R.B. et al. TUBB3//3III-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer Res 2015; 75: 2: 415-425.McCarroll J.A., Gan P.P., Erlich R.B. et al. TUBB3//3III-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer Res 2015; 75: 2: 415-425.Jordan A., Hadfield J.A., Lawrence N.J. et al. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998; 18: 4: 259-296.Jordan A., Hadfield J.A., Lawrence N.J. et al. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998; 18: 4: 259-296.Karki R., Mariani M., Andreoli M. et al. βIII-Tubulin: biomarker of taxane resistance or drug target? Expert Opin Ther Targets 2013; 17: 4: 461-472.Karki R., Mariani M., Andreoli M. et al. βIII-Tubulin: biomarker of taxane resistance or drug target? Expert Opin Ther Targets 2013; 17: 4: 461-472.Freedman H., Huzil J.T., Luchko T. et al. Identification and characterization of an intermediate taxol binding site within microtubule nanopores and a mechanism for tubulin isotype binding selectivity. J Chem Inf Model 2009; 49: 2: 424-436.Freedman H., Huzil J.T., Luchko T. et al. Identification and characterization of an intermediate taxol binding site within microtubule nanopores and a mechanism for tubulin isotype binding selectivity. J Chem Inf Model 2009; 49: 2: 424-436.Andreoli M., Persico M., Kumar A. et al. Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. J Med Chem 2014; 57: 19: 7916-7932.Andreoli M., Persico M., Kumar A. et al. Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. J Med Chem 2014; 57: 19: 7916-7932.Raspaglio G., Filippetti F., Prislei S. et al. Hypoxia induces class III beta-tubulin gene expression by HIF-1alpha binding to its 3' flanking region. Gene 2008; 409: 1-2: 100-108.Raspaglio G., Filippetti F., Prislei S. et al. Hypoxia induces class III beta-tubulin gene expression by HIF-1alpha binding to its 3' flanking region. Gene 2008; 409: 1-2: 100-108.Raspaglio G., De Maria I., Filippetti F. et al. HuR regulates beta-tubulin isotype expression in ovarian cancer. Cancer Res 2010; 70: 14: 5891-5900.Raspaglio G., De Maria I., Filippetti F. et al. HuR regulates beta-tubulin isotype expression in ovarian cancer. Cancer Res 2010; 70: 14: 5891-5900.Mozzetti S., Martinelli E., Raspaglio G. et al. Gli family transcription factors are drivers of patupilone resistance in ovarian cancer. Biochem Pharmacol 2012; 84: 11: 1409-1418.Mozzetti S., Martinelli E., Raspaglio G. et al. Gli family transcription factors are drivers of patupilone resistance in ovarian cancer. Biochem Pharmacol 2012; 84: 11: 1409-1418.Saussede-Aim J., Matera E.L., Ferlini C. et al. Beta3-tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-recep-tor dependent pathway. Cell Motil Cytoskeleton 2009; 66: 7: 378-388.Saussede-Aim J., Matera E.L., Ferlini C. et al. Beta3-tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-recep-tor dependent pathway. Cell Motil Cytoskeleton 2009; 66: 7: 378-388.De Gendt K., Denolet E., Willems A. et al. Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells. Biol Reprod 2011; 85: 5: 934-945.De Gendt K., Denolet E., Willems A. et al. Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells. Biol Reprod 2011; 85: 5: 934-945.Mariani M., Zannoni G.F., Sioletic S. et al. Gender influences the class III and V /З-tubulin ability to predict poor outcome in colorectal cancer. Clin Cancer Res 2012; 18: 10: 2964-2975.Mariani M., Zannoni G.F., Sioletic S. et al. Gender influences the class III and V /З-tubulin ability to predict poor outcome in colorectal cancer. Clin Cancer Res 2012; 18: 10: 2964-2975.Terry S., Ploussard G., Allory Y. et al. Increased expression of class III beta-tubulin in castration-resistant human prostate cancer. Br J Cancer 2009; 101: 6: 951-956.Terry S., Ploussard G., Allory Y. et al. Increased expression of class III beta-tubulin in castration-resistant human prostate cancer. Br J Cancer 2009; 101: 6: 951-956.Shibazaki M., Maesawa C., Akasaka K. et al. Transcriptional and post-transcriptional regulation of ßIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells Oncol 2012; 40: 3: 695-702.Shibazaki M., Maesawa C., Akasaka K. et al. Transcriptional and post-transcriptional regulation of ßIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells Oncol 2012; 40: 3: 695-702.Mariani M., Karki R., Spennato M. et al. Class III /в-tubulin in normal and cancer tissues Gene 2015; 563: 2: 109-114.Mariani M., Karki R., Spennato M. et al. Class III /в-tubulin in normal and cancer tissues Gene 2015; 563: 2: 109-114.Tischfield M.A., Baris H.N., Wu C. et al. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 2010; 140: 1: 74-87.Tischfield M.A., Baris H.N., Wu C. et al. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 2010; 140: 1: 74-87.Katsetos C.D., Drâber P. Tubulins as therapeutic targets in cancer: from bench to bedside. Curr Pharm Des 2012; 18: 19: 2778-2792.Katsetos C.D., Drâber P. Tubulins as therapeutic targets in cancer: from bench to bedside. Curr Pharm Des 2012; 18: 19: 2778-2792.Lewis S.A., Cowan N.J. Complex regulation and functional versatility of mammalian alpha- and beta-tubulin isotypes during the differentiation of testis and muscle cells. J Cell Biol 1988; 106: 6: 2023-2033.Lewis S.A., Cowan N.J. Complex regulation and functional versatility of mammalian alpha- and beta-tubulin isotypes during the differentiation of testis and muscle cells. J Cell Biol 1988; 106: 6: 2023-2033.Peknicova J., Kubatova A., Sulimenko V. et al. Differential subcellular distribution of tubulin epitopes in boar spermatozoa: recognition of class III-tubulin epitope in sperm tail. Biol Reprod 2001; 65: 672-679.Peknicova J., Kubatova A., Sulimenko V. et al. Differential subcellular distribution of tubulin epitopes in boar spermatozoa: recognition of class III-tubulin epitope in sperm tail. Biol Reprod 2001; 65: 672-679.Locher H., Frijns J.H., Huisman M.A., de Sousa Lopes S.M. TUBB3: Neuronal Marker or Melanocyte Mimic? Cell Transplant 2014; 23: 11: 1471-1473.Locher H., Frijns J.H., Huisman M.A., de Sousa Lopes S.M. TUBB3: Neuronal Marker or Melanocyte Mimic? Cell Transplant 2014; 23: 11: 1471-1473.Yu H., Fang D., Kumar S.M. et al. Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 2006; 168: 6: 1879-1888.Yu H., Fang D., Kumar S.M. et al. Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 2006; 168: 6: 1879-1888.Katsetos C.D., Del Valle L., Geddes J.F. et al. Localization of the neuronal class III beta-tubulin in oligodendrogliomas: comparison with Ki-67 proliferative index and 1p/19q status. J Neuropathol Exp Neurol 2002; 61: 4: 307-320.Katsetos C.D., Del Valle L., Geddes J.F. et al. Localization of the neuronal class III beta-tubulin in oligodendrogliomas: comparison with Ki-67 proliferative index and 1p/19q status. J Neuropathol Exp Neurol 2002; 61: 4: 307-320.Katsetos C.D., Del Valle L., Legido A. et al. On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak. Acta Neuropathol. 2003; 105: 1: 1-13.Katsetos C.D., Del Valle L., Legido A. et al. On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak. Acta Neuropathol. 2003; 105: 1: 1-13.Packer R.J., Sutton L.N., Rorke L.B. et al. Prognostic importance of cellular differentiation in medulloblastoma of childhood. J Neurosurg 1984; 61: 2: 296-301.Packer R.J., Sutton L.N., Rorke L.B. et al. Prognostic importance of cellular differentiation in medulloblastoma of childhood. J Neurosurg 1984; 61: 2: 296-301.Ikota H., Kinjo S., Yokoo H. et al. Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology. Acta Neuropathol 2006; 111: 5: 475-482.Ikota H., Kinjo S., Yokoo H. et al. Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology. Acta Neuropathol 2006; 111: 5: 475-482.Katsetos C.D., Del Valle L., Geddes J.F. et al. Aberrant localization of the neuronal class III beta-tubulin in astrocytomas. Arch Pathol Lab Med 2001; 125: 5: 613-624.Katsetos C.D., Del Valle L., Geddes J.F. et al. Aberrant localization of the neuronal class III beta-tubulin in astrocytomas. Arch Pathol Lab Med 2001; 125: 5: 613-624.Katsetos C.D., Draber P., Kavallaris M. Targeting /βIII-tubulin in glioblastoma multiforme: from cell biology and histopathology to cancer therapeutics. Anticancer Agents Med Chem 2011; 11: 8: 719-728.Katsetos C.D., Draber P., Kavallaris M. Targeting /βIII-tubulin in glioblastoma multiforme: from cell biology and histopathology to cancer therapeutics. Anticancer Agents Med Chem 2011; 11: 8: 719-728.Jirâsek T., Pisarikova E., Viklicky V. et al. Expression of class III beta-tubulin in malignant epithelial tumours: an immunohistochemical study using TU-20 and TuJ-1 antibodies. Folia Histochem Cytobiol 2007; 45: 1: 41-45.Jirâsek T., Pisarikova E., Viklicky V. et al. Expression of class III beta-tubulin in malignant epithelial tumours: an immunohistochemical study using TU-20 and TuJ-1 antibodies. Folia Histochem Cytobiol 2007; 45: 1: 41-45.Kavallaris M., Kuo D.Y., Burkhart C.A. et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997; 100: 5: 1282-1293.Kavallaris M., Kuo D.Y., Burkhart C.A. et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997; 100: 5: 1282-1293.Mozzetti S., Ferlini C., Concolino P. et al. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res 2005; 11: 1: 298-305.Mozzetti S., Ferlini C., Concolino P. et al. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res 2005; 11: 1: 298-305.Ferrandina G., Zannoni G.F., Martinelli E. et al. Class III -Tubulin Overexpression Is a Marker of Poor Clinical Outcome in Advanced Ovarian Cancer Patients. Clin Cancer Res 2006; 12: 9: 2774-2779.Ferrandina G., Zannoni G.F., Martinelli E. et al. Class III -Tubulin Overexpression Is a Marker of Poor Clinical Outcome in Advanced Ovarian Cancer Patients. Clin Cancer Res 2006; 12: 9: 2774-2779.Su D., Smith S.M., Preti M. et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer 2009; 115: 11: 2453-2463.Su D., Smith S.M., Preti M. et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer 2009; 115: 11: 2453-2463.Umezu T., Shibata K., Kajiyama H. et al. Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III beta-tubulin. Int J Gynecol Pathol 2008; 27: 2: 207-212.Umezu T., Shibata K., Kajiyama H. et al. Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III beta-tubulin. Int J Gynecol Pathol 2008; 27: 2: 207-212.Aoki D., Oda Y., Hattori S. et al. Overexpression of class III beta-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma. Clin Cancer Res 2009; 15: 4: 1473-1480.Aoki D., Oda Y., Hattori S. et al. Overexpression of class III beta-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma. Clin Cancer Res 2009; 15: 4: 1473-1480.Jakobsen J.N., Santoni-Rugiu E., Sorensen J.B. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer Chemother Pharmacol 2014; 73: 1: 43-51.Jakobsen J.N., Santoni-Rugiu E., Sorensen J.B. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer Chemother Pharmacol 2014; 73: 1: 43-51.Jakobsen J.N., Santoni-Rugiu E. S.J.B. Use of TUBßIII for patient stratification and prognosis in lung cancer. Lung Cancer Manag 2015; 4: 2: 97-110.Jakobsen J.N., Santoni-Rugiu E. S.J.B. Use of TUBßIII for patient stratification and prognosis in lung cancer. Lung Cancer Manag 2015; 4: 2: 97-110.Lebok P., Öztürk M., Heilenkötter U. et al. High levels of class III ß-tubulin expression are associated with aggressive tumor features in breast cancer. Oncol Lett 2016; 11: 3: 1987-1994.Lebok P., Öztürk M., Heilenkötter U. et al. High levels of class III ß-tubulin expression are associated with aggressive tumor features in breast cancer. Oncol Lett 2016; 11: 3: 1987-1994.Kanojia D., Morshed R.A., Zhang L. et al. III-Tubulin Regulates Breast Cancer Metastases to the Brain. Mol Cancer Ther 2015; 14: 5: 1152-1161.Kanojia D., Morshed R.A., Zhang L. et al. III-Tubulin Regulates Breast Cancer Metastases to the Brain. Mol Cancer Ther 2015; 14: 5: 1152-1161.Urano N., Fujiwara Y., Doki Y. et al. Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer. Int J Oncol 2006; 28: 2: 375-381.Urano N., Fujiwara Y., Doki Y. et al. Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer. Int J Oncol 2006; 28: 2: 375-381.Gao J., Lu M., Yu J.W. et al. Thymidine Phosphorylase/ß-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. BMC Cancer. 2011; 11: 1: 177.Gao J., Lu M., Yu J.W. et al. Thymidine Phosphorylase/ß-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. BMC Cancer. 2011; 11: 1: 177.Jirâsek T., Cipro S., Musilovâ A. et al. Expression of class III beta-tubu-lin in colorectal carcinomas: an immunohistochemical study using TU-20 & TuJ-1 antibody. Indian J Med Res 2009; 129: 1: 89-94.Jirâsek T., Cipro S., Musilovâ A. et al. Expression of class III beta-tubu-lin in colorectal carcinomas: an immunohistochemical study using TU-20 & TuJ-1 antibody. Indian J Med Res 2009; 129: 1: 89-94.Sun H., Shi L., He X., Zheng S. Expressions of TUBB3 and gamma-synuclein in colorectal adenocarcinoma and their clinical significance. Zhonghua Yi Xue Za Zhi 2015; 95: 1242-1244.Sun H., Shi L., He X., Zheng S. Expressions of TUBB3 and gamma-synuclein in colorectal adenocarcinoma and their clinical significance. Zhonghua Yi Xue Za Zhi 2015; 95: 1242-1244.Портянко А.С. Ремоделирование цитоскелета в патогенезе и прогрессии аденокарциномы и хронических воспалительных заболеваний толстой кишки: дис.. д-ра. биол. наук: 14.03.02 Минск 2016: 43.Портянко А.С. Ремоделирование цитоскелета в патогенезе и прогрессии аденокарциномы и хронических воспалительных заболеваний толстой кишки: дис.. д-ра. биол. наук: 14.03.02 Минск 2016: 43.Egevad L., Valdman A., Wiklund N.P. et al. Beta-tubulin III expression in prostate cancer Scand J Urol Nephrol 2010; 44: 6: 371-377.Egevad L., Valdman A., Wiklund N.P. et al. Beta-tubulin III expression in prostate cancer Scand J Urol Nephrol 2010; 44: 6: 371-377.Ploussard G., Terry S., Maillé P. et al. Class III beta-tubulin expression predicts prostate tumor aggressiveness and patient response to docetaxel-based chemotherapy. Cancer Res 2010; 70: 22: 9253-9264.Ploussard G., Terry S., Maillé P. et al. Class III beta-tubulin expression predicts prostate tumor aggressiveness and patient response to docetaxel-based chemotherapy. Cancer Res 2010; 70: 22: 9253-9264.Hinsch A., Chaker A., Burdelski C. et al. /βIII-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer. Hum Pathol 2017; 61: 210-220.Hinsch A., Chaker A., Burdelski C. et al. /βIII-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer. Hum Pathol 2017; 61: 210-220.Quaas A., Rahvar A.H., Burdelski C. et al. /βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma World J Urol 2015; 33: 10: 1561-1569.Quaas A., Rahvar A.H., Burdelski C. et al. /βIII-tubulin overexpression is linked to aggressive tumor features and shortened survival in clear cell renal cell carcinoma World J Urol 2015; 33: 10: 1561-1569.Ferrandina G., Martinelli E., Zannoni G.F. et al. Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol Oncol 2007; 104: 2: 326-330.Ferrandina G., Martinelli E., Zannoni G.F. et al. Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol Oncol 2007; 104: 2: 326-330.Koh Y., Kim T.M., Jeon Y.K. et al. Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma. Ann Oncol 2009; 20: 8: 1414-1419.Koh Y., Kim T.M., Jeon Y.K. et al. Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma. Ann Oncol 2009; 20: 8: 1414-1419.Kaira K., Serizawa M., Koh Y. et al. Expression of Excision Repair Cross-Complementation Group 1, Breast Cancer Susceptibility 1, and ßIII-Tubulin in Thymic Epithelial Tumors. J Thorac Oncol 2011; 6: 3: 606-613.Kaira K., Serizawa M., Koh Y. et al. Expression of Excision Repair Cross-Complementation Group 1, Breast Cancer Susceptibility 1, and ßIII-Tubulin in Thymic Epithelial Tumors. J Thorac Oncol 2011; 6: 3: 606-613.Akasaka K., Maesawa C., Shibazaki M. et al. Loss of class III beta-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells. J Invest Dermatol 2009; 129: 6: 1516-1526.Akasaka K., Maesawa C., Shibazaki M. et al. Loss of class III beta-tubulin induced by histone deacetylation is associated with chemosensitivity to paclitaxel in malignant melanoma cells. J Invest Dermatol 2009; 129: 6: 1516-1526.Miyamoto A., Akasaka K., Oikawa H. et al. Immunohistochemical study of HER2 and TUBB3 proteins in extramammary Paget disease. Am J Dermatopathol 2010; 32: 6: 578-585.Miyamoto A., Akasaka K., Oikawa H. et al. Immunohistochemical study of HER2 and TUBB3 proteins in extramammary Paget disease. Am J Dermatopathol 2010; 32: 6: 578-585.Ishida M., Kushima R., Okabe H. Aberrant expression of class III beta-tubulin in basal cell carcinoma of the skin. Oncol Rep 2009; 22: 4: 733-737.Ishida M., Kushima R., Okabe H. Aberrant expression of class III beta-tubulin in basal cell carcinoma of the skin. Oncol Rep 2009; 22: 4: 733-737.Powell S., Kaizer A., Koopmeiners J.S. et al. High expression of class IIIß tubulin in small cell lung carcinoma. Oncol Lett 2013; 7: 2: 405-410.Powell S., Kaizer A., Koopmeiners J.S. et al. High expression of class IIIß tubulin in small cell lung carcinoma. Oncol Lett 2013; 7: 2: 405-410.Ting S, Mairinger F.D, Hager T. et al. ERCC1, MLH1, MSH2, MSH6, and betaIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural. mesothelioma. Clin Lung Cancer 2013; 14: 558-567.Ting S, Mairinger F.D, Hager T. et al. ERCC1, MLH1, MSH2, MSH6, and betaIII-tubulin: resistance proteins associated with response and outcome to platinum-based chemotherapy in malignant pleural. mesothelioma. Clin Lung Cancer 2013; 14: 558-567.Yoon S.O. et al. Class III beta-tubulin shows unique expression patterns in a variety of neoplastic and non-neoplastic lymphoproliferative disorders. Am. J. Surg. Pathol. 2010; 34: 5: 645-655.Yoon S.O. et al. Class III beta-tubulin shows unique expression patterns in a variety of neoplastic and non-neoplastic lymphoproliferative disorders. Am. J. Surg. Pathol. 2010; 34: 5: 645-655.Okuda K., Sasaki H., Dumontet C. et al. Expression of excision repair cross-complementation group 1 and class III beta-tubulin predict survival after chemotherapy for completely resected non-small cell lung cancer. Lung Cancer 2008; 62: 1: 105-112.Okuda K., Sasaki H., Dumontet C. et al. Expression of excision repair cross-complementation group 1 and class III beta-tubulin predict survival after chemotherapy for completely resected non-small cell lung cancer. Lung Cancer 2008; 62: 1: 105-112.Kang C.H., Jang B.G., Kim D.W. et al. The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer 2010; 68: 3: 478-483.Kang C.H., Jang B.G., Kim D.W. et al. The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer 2010; 68: 3: 478-483.Azuma K., Sasada T., Kawahara A. et al. Expression of ERCC1 and class III β-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel. Lung Cancer 2009; 64: 3: 326-333.Azuma K., Sasada T., Kawahara A. et al. Expression of ERCC1 and class III β-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel. Lung Cancer 2009; 64: 3: 326-333.Ikeda S., Takabe K., Suzuki K. Expression of ERCC1 and class IIIbeta tubulin for predicting effect of carboplatin/paclitaxel in patients with advanced inoperable non-small cell lung cancer. Pathol Int 2009; 59: 12: 863-867.Ikeda S., Takabe K., Suzuki K. Expression of ERCC1 and class IIIbeta tubulin for predicting effect of carboplatin/paclitaxel in patients with advanced inoperable non-small cell lung cancer. Pathol Int 2009; 59: 12: 863-867.Zhang Q., Zhu X., Zhang L. et al. A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 2014; 74: 4: 839-846.Zhang Q., Zhu X., Zhang L. et al. A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer. Cancer Chemother Pharmacol 2014; 74: 4: 839-846.Chen X., Wu J., Lu H. et al. Measuring ß-tubulin III, Bcl-2, and ERCC1 improves pathological complete remission predictive accuracy in breast cancer. Cancer Sci 2012; 103: 2: 262-268.Chen X., Wu J., Lu H. et al. Measuring ß-tubulin III, Bcl-2, and ERCC1 improves pathological complete remission predictive accuracy in breast cancer. Cancer Sci 2012; 103: 2: 262-268.Leandro-Garcfa L.J., Leskelä S., Landa I. et al. Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cytoskeleton (Hoboken) 2010; 67: 4: 214-223.Leandro-Garcfa L.J., Leskelä S., Landa I. et al. Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cytoskeleton (Hoboken) 2010; 67: 4: 214-223.Ishida M., Kushima R., Okabe H. Aberrant expression of class III beta-tubulin in basal cell carcinoma of the skin. Oncol Rep 2009; 22: 4: 733-737.Ishida M., Kushima R., Okabe H. Aberrant expression of class III beta-tubulin in basal cell carcinoma of the skin. Oncol Rep 2009; 22: 4: 733-737.Orfanidis K., Wäster P., Lundmark K. et al. Evaluation of tubulinß-3 as a novel senescence-associated gene in melanocytic malignant transformation. Pigment Cell Melanoma Res 2017; 30: 2: 243-254.Orfanidis K., Wäster P., Lundmark K. et al. Evaluation of tubulinß-3 as a novel senescence-associated gene in melanocytic malignant transformation. Pigment Cell Melanoma Res 2017; 30: 2: 243-254.Мамичев И.А., Богуш Т.А., Дудко Е. А. и др. Иммунофлуоресцентный анализ экспрессии бета-III тубулина в опухолевой и окружающей нормальной ткани пациентов с немелкоклеточным раком легкого. Росс биотер журнал. - 2016. - Т. 15. - № 2. - С. 16-18.Мамичев И.А., Богуш Т.А., Дудко Е. А. и др. Иммунофлуоресцентный анализ экспрессии бета-III тубулина в опухолевой и окружающей нормальной ткани пациентов с немелкоклеточным раком легкого. Росс биотер журнал. - 2016. - Т. 15. - № 2. - С. 16-18.

The authors declare that there are no conflicts of interest present.