Melanoma cell sensitivity to Docetaxel-induced apoptosis is determined by class III β-tubulin levels

Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
FEBS Letters (Impact Factor: 3.17). 02/2008; 582(2):267-72. DOI: 10.1016/j.febslet.2007.12.014
Source: PubMed


We have previously shown that Docetaxel-induced variable degrees of apoptosis in melanoma. In this report, we studied the beta-tubulin repertoire of melanoma cell lines and show that class III beta-tubulin expression correlated with Docetaxel-resistance. Sensitive cells showed low levels of class III beta-tubulin with little microtubular incorporation, whereas class III beta-tubulin expression was higher in resistant cells and was incorporated into the cytoskeleton. As proof of concept, abrogation of class III by siRNA reverted Docetaxel-resistant cells to a sensitive phenotype, restoring the microtubular polymerisation response and promoting high levels of apoptosis through Bax activation. These results suggest that phenotypic expression of beta-tubulin class III in melanoma may help identify patients with melanoma that can respond to taxanes.

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Available from: Charles E. De Bock
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    • "The nucleofaction protocol for plasmid transfection was optimised using a GFP-construct with efficacies of 47 and 70% being achieved after 24 h transfection in MCF-7 and MDA-MB-231 cells, respectively. siRNA nucleofection was carried out using a pre-optimised protocol (Mhaidat et al, 2008). Briefly, the cells were trypsinised and washed with PBS. "
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    • "In particular, EGC up-regulated the expression of TUBB3, a gene encoding the class III isotype of β-tubulin. Silencing of class III β-tubulin by siRNA reverted anti-cancer agent-resistant cells to a sensitive phenotype and promoted apoptosis [78,79]. Conversely, EGC inhibited the expression of CARD12 which encodes the CARD12 protein, a member of the CED4/Apaf-1 family and known to induce apoptosis when expressed in cells [80,81]. "
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    • "Recently, Mhaidat et al. (2008) demonstrated that sensitivity to docetaxel-induced apoptosis correlates with TUBB3 protein expression in malignant melanoma cell lines. Hence, they suggested that overexpression of TUBB3 protein might help identify patients with melanoma who will respond to taxane derivatives (Mhaidat et al., 2008). However, TUBB3 expression has never been systematically examined in malignant melanomas and normal melanocytes. "
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