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: 3.34). 02/2008; 582(2):267-72. DOI: 10.1016/j.febslet.2007.12.014
Source: PubMed

ABSTRACT 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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