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

Abstract

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.

Screening Anti-Cancer Drugs against Tubulin using Catch-and-Release Electrospray Ionization Mass Spectrometry

“…The reason for this is that tubulin is an abundant protein common to all cells in the body. However, the distribution of tubulin isotypes is different for all cell types and especially for cancer cells [50]. Therefore, the idea of targeting an isotype of tubulin that is highly expressed in cancer cells and much less so in normal cells would lead to an optimization of treatment efficacy and minimization of side effects [51].…”

Mitotic Centromere-associated Kinesin (MCAK) Mediates Paclitaxel Resistance

“…Tax 11-6 is a cell line with an E77K substitution in ␣-tubulin that was shown previously to have reduced microtubule polymer and an elevated frequency of microtubule detachment (23). HA␤3-3 is a cell line that was created by transfecting wild-type CHO cells with a plasmid encoding HA-tagged ␤3-tubulin, an isotype whose expression is normally restricted to brain (10,11). The transfected cells were found to have reduced microtubule polymer and to be paclitaxel-resistant and paclitaxel-dependent (14).…”

“…Some of these isotypes are ubiquitously expressed, whereas others (e.g. ␤3, ␤4a, and ␤6) are restricted to specific tissues (10,11). In addition, most cultured cell lines express a small subset of these isotypes; for example, CHO cell microtubules are composed of 70% ␤1, 25% ␤4b, and 5% ␤5 (12).…”

The miR-200 family controls -tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients

“…Paclitaxel binds to b-tubulin, leading to cellular microtubules stabilization, mitotic arrest, and finally to cell death. In humans, there are at least eight different isotypes of b-tubulin, which exhibit an altered expression pattern in tumoral tissue (Leandro-Garcia et al 2010). In ovarian carcinoma, high protein levels of classes I and IV, intermediate levels of class III, and low levels of class II b-tubulin have been reported (Ohishi et al 2007).…”