Tumoral and tissue-specific expression of the major human beta-tubulin isotypes.
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.
Leandro-García
Luis J
LJ
Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Melchor Fernández Almagro n 3, Madrid, Spain.
Leskelä
Susanna
S
Landa
Iñigo
I
Montero-Conde
Cristina
C
López-Jiménez
Elena
E
Letón
Rocío
R
Cascón
Alberto
A
Robledo
Mercedes
M
Rodríguez-Antona
Cristina
C
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000235:genetics*
D020033:Protein Isoforms; D012333:RNA, Messenger; D014404:Tubulin