No coin nor oath required. For personal study only.
Aims: Docetaxel is one of the most effective single agents used to treat breast cancer. However, up to 50% of patients can be resistant to it and the mechanisms of resistance are poorly understood. The cellular target of docetaxel is the microtubule, binding to beta-tubulin subunits. Altered expression of beta-tubulin subtypes have been shown to be involved in ovarian and lung cancer resistant to other taxanes. Therefore, this study aimed to investigate the role of beta-tubulins in development of resistance to docetaxel in breast cancer cells. Methods: Breast cancer cell line MCF-7 was made resistant to docetaxel by short term in vitro exposure to increasing concentrations of docetaxel over 50 weeks. Total RNA was prepared from the docetaxel-resistant and -sensitive cells, and then reverse transcribed into cDNA. Primers specific for Class I, II, III and VI beta-tubulin were used for reverse transcriptase-polymerase chain reaction analysis. In addition, protein expression was determined by Western analysis. Results: Class I, II and III beta-tubulin were over expressed in docetaxel-resistant MCF-7 cells (3•68 ± 0•7-, 1•75 ± 0•1-and 2•18 ± 0•42-fold, respectively) when compared with drug-sensitive parental cells. However, Class VI betatubulin was down regulated (0•28 ± 0•05). Gene expression differences of Class I and III beta-tubulin, at the RNA level, were confirmed by Western analysis (protein level).
The results from this study demonstrate over expression of Class I, II and III, and down regulation of Class VI beta-tubulin in docetaxel-resistant breast cancer cells. Such molecular alterations may represent a novel mechanism of resistance in breast cancer.
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