Tumoral and tissue-specific expression of the major human β-tubulin isotypes

The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on β‐tubulin binding, microtubule dynamics alteration, and cell division blockage. The expres...

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Published inCytoskeleton (Hoboken, N.J.) Vol. 67; no. 4; pp. 214 - 223
Main Authors Leandro-García, Luis J., Leskelä, Susanna, Landa, Iñigo, Montero-Conde, Cristina, López-Jiménez, Elena, Letón, Rocío, Cascón, Alberto, Robledo, Mercedes, Rodríguez-Antona, Cristina
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.04.2010
Subjects
Online AccessGet full text
ISSN1949-3584
1949-3592
1949-3592
DOI10.1002/cm.20436

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Abstract The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on β‐tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex β‐tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT‐PCR technique that accurately determines the mRNA expression of the eight human β‐tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell‐specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total β‐tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex β‐tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule‐binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley‐Liss, Inc.
AbstractList The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on β‐tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex β‐tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT‐PCR technique that accurately determines the mRNA expression of the eight human β‐tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell‐specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total β‐tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex β‐tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule‐binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley‐Liss, Inc.
The beta-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on beta-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex beta-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human beta-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total beta-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex beta-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response.
The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on β‐tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex β‐tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT‐PCR technique that accurately determines the mRNA expression of the eight human β‐tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1 (VI) was hematopoietic cell‐specific, and TUBB2A (IIa) , TUBB2B (IIb) , TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total β‐tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex β‐tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule‐binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley‐Liss, Inc.
The beta-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on beta-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex beta-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human beta-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total beta-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex beta-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response.The beta-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on beta-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex beta-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human beta-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total beta-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex beta-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response.
Author Leandro-García, Luis J.
Leskelä, Susanna
Letón, Rocío
López-Jiménez, Elena
Cascón, Alberto
Montero-Conde, Cristina
Rodríguez-Antona, Cristina
Robledo, Mercedes
Landa, Iñigo
Author_xml – sequence: 1
  givenname: Luis J.
  surname: Leandro-García
  fullname: Leandro-García, Luis J.
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 2
  givenname: Susanna
  surname: Leskelä
  fullname: Leskelä, Susanna
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 3
  givenname: Iñigo
  surname: Landa
  fullname: Landa, Iñigo
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 4
  givenname: Cristina
  surname: Montero-Conde
  fullname: Montero-Conde, Cristina
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 5
  givenname: Elena
  surname: López-Jiménez
  fullname: López-Jiménez, Elena
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 6
  givenname: Rocío
  surname: Letón
  fullname: Letón, Rocío
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 7
  givenname: Alberto
  surname: Cascón
  fullname: Cascón, Alberto
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 8
  givenname: Mercedes
  surname: Robledo
  fullname: Robledo, Mercedes
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
– sequence: 9
  givenname: Cristina
  surname: Rodríguez-Antona
  fullname: Rodríguez-Antona, Cristina
  email: cristina.rodriguez-antona@cnio.es
  organization: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain
BackLink https://www.ncbi.nlm.nih.gov/pubmed/20191564$$D View this record in MEDLINE/PubMed
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10.1073/pnas.83.12.4327
10.1158/1078-0432.298.11.1
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References Lopata MA, Cleveland DW. 1987. In vivo microtubules are copolymers of available beta-tubulin isotypes: localization of each of six vertebrate beta-tubulin isotypes using polyclonal antibodies elicited by synthetic peptide antigens. J Cell Biol 105: 1707-1720.
Cleveland DW. 1987. The multitubulin hypothesis revisited: what have we learned? J Cell Biol 104: 381-383.
Hasegawa S, Miyoshi Y, Egawa C, Ishitobi M, Taguchi T, Tamaki Y, Monden M, Noguchi S. 2003. Prediction of response to docetaxel by quantitative analysis of class I and III beta-tubulin isotype mRNA expression in human breast cancers. Clin Cancer Res 9: 2992-2997.
Havercroft JC, Cleveland DW. 1984. Programmed expression of beta-tubulin genes during development and differentiation of the chicken. J Cell Biol 99: 1927-1935.
Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
Cucchiarelli V, Hiser L, Smith H, Frankfurter A, Spano A, Correia JJ, Lobert S. 2008. Beta-tubulin isotype classes II and V expression patterns in nonsmall cell lung carcinomas. Cell Motil Cytoskeleton 65: 675-685.
Panda D, Miller HP, Banerjee A, Ludueña RF, Wilson L. 1994. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci USA 91: 11358-11362.
Arai K, Shibutani M, Matsuda H. 2002. Distribution of the class II beta-tubulin in developmental and adult rat tissues. Cell Motil Cytoskeleton 52: 174-182.
Shalli K, Brown I, Heys SD, Schofield AC. 2005. Alterations of beta-tubulin isotypes in breast cancer cells resistant to docetaxel. Faseb J 19: 1299-1301.
Andre F, Broglio K, Roche H, Martin M, Mackey JR, Penault-Llorca F, Hortobagyi GN, Pusztai L. 2008. Estrogen receptor expression and efficacy of docetaxel-containing adjuvant chemotherapy in patients with node-positive breast cancer: results from a pooled analysis. J Clin Oncol 26: 2636-2643.
Ohishi Y, Oda Y, Basaki Y, Kobayashi H, Wake N, Kuwano M, Tsuneyoshi M. 2007. Expression of beta-tubulin isotypes in human primary ovarian carcinoma. Gynecol Oncol 105: 586-592.
Kavallaris M, Tait AS, Walsh BJ, He L, Horwitz SB, Norris MD, Haber M. 2001. Multiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells. Cancer Res 61: 5803-5809.
Wang D, Villasante A, Lewis SA, Cowan NJ. 1986. The mammalian beta-tubulin repertoire: hematopoietic expression of a novel, heterologous beta-tubulin isotype. J Cell Biol 103: 1903-1910.
Escuin D, Burke PA, McMahon-Tobin G, Hembrough T, Wang Y, Alcaraz AA, Leandro-García LJ, Rodríguez-Antona C, Snyder JP, LaVallee TM, et al. 2009. The hematopoietic-specific 1-tubulin is naturally resistant to 2-Methoxyestradiol and protects patients from drug-induced myelosuppression. Cell Cycle 8: 3914-3924.
Hiser L, Aggarwal A, Young R, Frankfurter A, Spano A, Correia JJ, Lobert S. 2006. Comparison of beta-tubulin mRNA and protein levels in 12 human cancer cell lines. Cell Motil Cytoskeleton 63: 41-52.
Risinger AL, Giles FJ, Mooberry SL. 2009. Microtubule dynamics as a target in oncology. Cancer Treat Rev 35: 255-261.
Ferrandina G, Zannoni GF, Martinelli E, Paglia A, Gallotta V, Mozzetti S, Scambia G, Ferlini C. 2006. Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res 12: 2774-2779.
Berrieman HK, Lind MJ, Cawkwell L. 2004. Do beta-tubulin mutations have a role in resistance to chemotherapy? Lancet Oncol 5: 158-164.
Conforti R, Boulet T, Tomasic G, Taranchon E, Arriagada R, Spielmann M, Ducourtieux M, Soria JC, Tursz T, Delaloge S, Michiels S, Andre F. 2007. Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study from two randomized trials. Ann Oncol 18: 1477-1483.
Nicoletti MI, Valoti G, Giannakakou P, Zhan Z, Kim JH, Lucchini V, Landoni F, Mayo JG, Giavazzi R, Fojo T. 2001. Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-Anticancer Drug Screen: correlation with sensitivity to microtubule active agents. Clin Cancer Res 7: 2912-2922.
Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, Gallo D, Martinelli E, Ranelletti FO, Ferrandina G, et al. 2005. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res 11: 298-305.
Seve P, Isaac S, Tredan O, Souquet PJ, Pacheco Y, Perol M, Lafanechere L, Penet A, Peiller EL, Dumontet C. 2005. Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res 11: 5481-5486.
Verrills NM, Flemming CL, Liu M, Ivery MT, Cobon GS, Norris MD, Haber M, Kavallaris M. 2003. Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions. Chem Biol 10: 597-607.
Hari M, Yang H, Zeng C, Canizales M, Cabral F. 2003. Expression of class III beta-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil Cytoskeleton 56: 45-56.
Dozier JH, Hiser L, Davis JA, Thomas NS, Tucci MA, Benghuzzi HA, Frankfurter A, Correia JJ, Lobert S. 2003. Beta class II tubulin predominates in normal and tumor breast tissues. Breast Cancer Res 5: R157-R169.
Sullivan KF, Cleveland DW. 1986. Identification of conserved isotype-defining variable region sequences for four vertebrate beta tubulin polypeptide classes. Proc Natl Acad Sci USA 83: 4327-4331.
Bhattacharya R, Cabral F. 2004. A ubiquitous beta-tubulin disrupts microtubule assembly and inhibits cell proliferation. Mol Biol Cell 15: 3123-3131.
Blade K, Menick DR, Cabral F. 1999. Overexpression of class I, II or IVb beta-tubulin isotypes in CHO cells is insufficient to confer resistance to paclitaxel. J Cell Sci 112 ( Part 13): 2213-2221.
Seve P, Reiman T, Lai R, Hanson J, Santos C, Johnson L, Dabbagh L, Sawyer M, Dumontet C, Mackey JR. 2007b. Class III beta-tubulin is a marker of paclitaxel resistance in carcinomas of unknown primary site. Cancer Chemother Pharmacol 60: 27-34.
Cleveland DW, Joshi HC, Murphy DB. 1990. Tubulin site interpretation. Nature 344: 389.
Ludueña RF. 1998. Multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol 178: 207-275.
Ferrandina G, Martinelli E, Zannoni GF, Distefano M, Paglia A, Ferlini C, Scambia G. 2007. Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol Oncol 104: 326-330.
Giannakakou P, Gussio R, Nogales E, Downing KH, Zaharevitz D, Bollbuck B, Poy G, Sackett D, Nicolaou KC, Fojo T. 2000. A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. Proc Natl Acad Sci USA 97: 2904-2909.
Derry WB, Wilson L, Khan IA, Ludueña RF, Jordan MA. 1997. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry 36: 3554-3562.
Banerjee A, Roach MC, Trcka P, Ludueña RF. 1990. Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of beta-tubulin. J Biol Chem 265: 1794-1799.
Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, Poruchynsky MS. 1997. Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 272: 17118-17125.
Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, et al. 2006. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295: 1658-1667.
Verdier-Pinard P, Shahabi S, Wang F, Burd B, Xiao H, Goldberg GL, Orr GA, Horwitz SB. 2005. Detection of human betaV-tubulin expression in epithelial cancer cell lines by tubulin proteomics. Biochemistry 44: 15858-15870.
Gan PP, Kavallaris M. 2008. Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity. Cancer Res 68: 9817-9824.
Kamath K, Wilson L, Cabral F, Jordan MA. 2005. BetaIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem 280: 12902-12907.
Luchko T, Huzil JT, Stepanova M, Tuszynski J. 2008. Conformational analysis of the carboxy-terminal tails of human beta-tubulin isotypes. Biophys J 94: 1971-1982.
Sullivan KF, Havercroft JC, Machlin PS, Cleveland DW. 1986. Sequence and expression of the chicken beta 5- and beta 4-tubulin genes define a pair of divergent beta-tubulins with complementary patterns of expression. Mol Cell Biol 6: 4409-4418.
Seve P, Lai R, Ding K, Winton T, Butts C, Mackey J, Dumontet C, Dabbagh L, Aviel-Ronen S, Seymour L, et al. 2007a. Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR. 10. Clin Cancer Res 13: 994-999.
Verhey KJ, Gaertig J. 2007. The tubulin code. Cell Cycle 6: 2152-2160.
2007; 18
2007; 104
2007; 105
2002; 52
2006; 12
1987; 105
1997; 272
1987; 104
2006; 295
2004; 5
2008; 94
1990; 344
1990; 265
2001; 25
1998; 178
2005; 44
2003; 10
2003; 56
2007b; 60
2005; 280
2001; 61
2009; 35
2006; 63
2005; 19
1986; 103
1986; 83
2001; 7
2001
2004; 15
1997; 36
1984; 99
2007a; 13
2000; 97
2003; 9
1986; 6
2008; 26
2007; 6
2003; 5
2009; 8
2008; 68
2008; 65
1999; 112
1994; 91
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References_xml – reference: Panda D, Miller HP, Banerjee A, Ludueña RF, Wilson L. 1994. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci USA 91: 11358-11362.
– reference: Luchko T, Huzil JT, Stepanova M, Tuszynski J. 2008. Conformational analysis of the carboxy-terminal tails of human beta-tubulin isotypes. Biophys J 94: 1971-1982.
– reference: Verdier-Pinard P, Shahabi S, Wang F, Burd B, Xiao H, Goldberg GL, Orr GA, Horwitz SB. 2005. Detection of human betaV-tubulin expression in epithelial cancer cell lines by tubulin proteomics. Biochemistry 44: 15858-15870.
– reference: Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
– reference: Cleveland DW. 1987. The multitubulin hypothesis revisited: what have we learned? J Cell Biol 104: 381-383.
– reference: Andre F, Broglio K, Roche H, Martin M, Mackey JR, Penault-Llorca F, Hortobagyi GN, Pusztai L. 2008. Estrogen receptor expression and efficacy of docetaxel-containing adjuvant chemotherapy in patients with node-positive breast cancer: results from a pooled analysis. J Clin Oncol 26: 2636-2643.
– reference: Ludueña RF. 1998. Multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol 178: 207-275.
– reference: Cleveland DW, Joshi HC, Murphy DB. 1990. Tubulin site interpretation. Nature 344: 389.
– reference: Wang D, Villasante A, Lewis SA, Cowan NJ. 1986. The mammalian beta-tubulin repertoire: hematopoietic expression of a novel, heterologous beta-tubulin isotype. J Cell Biol 103: 1903-1910.
– reference: Nicoletti MI, Valoti G, Giannakakou P, Zhan Z, Kim JH, Lucchini V, Landoni F, Mayo JG, Giavazzi R, Fojo T. 2001. Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-Anticancer Drug Screen: correlation with sensitivity to microtubule active agents. Clin Cancer Res 7: 2912-2922.
– reference: Blade K, Menick DR, Cabral F. 1999. Overexpression of class I, II or IVb beta-tubulin isotypes in CHO cells is insufficient to confer resistance to paclitaxel. J Cell Sci 112 ( Part 13): 2213-2221.
– reference: Risinger AL, Giles FJ, Mooberry SL. 2009. Microtubule dynamics as a target in oncology. Cancer Treat Rev 35: 255-261.
– reference: Sullivan KF, Cleveland DW. 1986. Identification of conserved isotype-defining variable region sequences for four vertebrate beta tubulin polypeptide classes. Proc Natl Acad Sci USA 83: 4327-4331.
– reference: Gan PP, Kavallaris M. 2008. Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity. Cancer Res 68: 9817-9824.
– reference: Hiser L, Aggarwal A, Young R, Frankfurter A, Spano A, Correia JJ, Lobert S. 2006. Comparison of beta-tubulin mRNA and protein levels in 12 human cancer cell lines. Cell Motil Cytoskeleton 63: 41-52.
– reference: Verrills NM, Flemming CL, Liu M, Ivery MT, Cobon GS, Norris MD, Haber M, Kavallaris M. 2003. Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions. Chem Biol 10: 597-607.
– reference: Cucchiarelli V, Hiser L, Smith H, Frankfurter A, Spano A, Correia JJ, Lobert S. 2008. Beta-tubulin isotype classes II and V expression patterns in nonsmall cell lung carcinomas. Cell Motil Cytoskeleton 65: 675-685.
– reference: Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, Gallo D, Martinelli E, Ranelletti FO, Ferrandina G, et al. 2005. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res 11: 298-305.
– reference: Seve P, Isaac S, Tredan O, Souquet PJ, Pacheco Y, Perol M, Lafanechere L, Penet A, Peiller EL, Dumontet C. 2005. Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res 11: 5481-5486.
– reference: Hari M, Yang H, Zeng C, Canizales M, Cabral F. 2003. Expression of class III beta-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil Cytoskeleton 56: 45-56.
– reference: Dozier JH, Hiser L, Davis JA, Thomas NS, Tucci MA, Benghuzzi HA, Frankfurter A, Correia JJ, Lobert S. 2003. Beta class II tubulin predominates in normal and tumor breast tissues. Breast Cancer Res 5: R157-R169.
– reference: Giannakakou P, Gussio R, Nogales E, Downing KH, Zaharevitz D, Bollbuck B, Poy G, Sackett D, Nicolaou KC, Fojo T. 2000. A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. Proc Natl Acad Sci USA 97: 2904-2909.
– reference: Arai K, Shibutani M, Matsuda H. 2002. Distribution of the class II beta-tubulin in developmental and adult rat tissues. Cell Motil Cytoskeleton 52: 174-182.
– reference: Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, Poruchynsky MS. 1997. Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 272: 17118-17125.
– reference: Derry WB, Wilson L, Khan IA, Ludueña RF, Jordan MA. 1997. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry 36: 3554-3562.
– reference: Ferrandina G, Martinelli E, Zannoni GF, Distefano M, Paglia A, Ferlini C, Scambia G. 2007. Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol Oncol 104: 326-330.
– reference: Escuin D, Burke PA, McMahon-Tobin G, Hembrough T, Wang Y, Alcaraz AA, Leandro-García LJ, Rodríguez-Antona C, Snyder JP, LaVallee TM, et al. 2009. The hematopoietic-specific 1-tubulin is naturally resistant to 2-Methoxyestradiol and protects patients from drug-induced myelosuppression. Cell Cycle 8: 3914-3924.
– reference: Bhattacharya R, Cabral F. 2004. A ubiquitous beta-tubulin disrupts microtubule assembly and inhibits cell proliferation. Mol Biol Cell 15: 3123-3131.
– reference: Lopata MA, Cleveland DW. 1987. In vivo microtubules are copolymers of available beta-tubulin isotypes: localization of each of six vertebrate beta-tubulin isotypes using polyclonal antibodies elicited by synthetic peptide antigens. J Cell Biol 105: 1707-1720.
– reference: Banerjee A, Roach MC, Trcka P, Ludueña RF. 1990. Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of beta-tubulin. J Biol Chem 265: 1794-1799.
– reference: Sullivan KF, Havercroft JC, Machlin PS, Cleveland DW. 1986. Sequence and expression of the chicken beta 5- and beta 4-tubulin genes define a pair of divergent beta-tubulins with complementary patterns of expression. Mol Cell Biol 6: 4409-4418.
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– reference: Shalli K, Brown I, Heys SD, Schofield AC. 2005. Alterations of beta-tubulin isotypes in breast cancer cells resistant to docetaxel. Faseb J 19: 1299-1301.
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Snippet The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several...
The beta-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns....
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SubjectTerms Gene Expression Regulation, Neoplastic
Humans
isotypes
microtubule-binding drugs
microtubules
Neoplasms - genetics
Organ Specificity
Protein Isoforms - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
RNA, Messenger - genetics
Tubulin - genetics
β-tubulin
Title Tumoral and tissue-specific expression of the major human β-tubulin isotypes
URI https://api.istex.fr/ark:/67375/WNG-PJTXTL96-G/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcm.20436
https://www.ncbi.nlm.nih.gov/pubmed/20191564
https://www.proquest.com/docview/733803832
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