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Melanoma cell sensitivity to Docetaxel‐induced apoptosis is determined by class III β‐tubulin levels
Author(s) -
Mhaidat Nizar M.,
Thorne Rick F.,
de Bock Charles Edo,
Zhang Xu Dong,
Hersey Peter
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.12.014
Subject(s) - docetaxel , melanoma , tubulin , apoptosis , microtubule , phenotype , cancer research , cell culture , biology , chemistry , microbiology and biotechnology , chemotherapy , genetics , gene
We have previously shown that Docetaxel‐induced variable degrees of apoptosis in melanoma. In this report, we studied the β‐tubulin repertoire of melanoma cell lines and show that class III β‐tubulin expression correlated with Docetaxel‐resistance. Sensitive cells showed low levels of class III β‐tubulin with little microtubular incorporation, whereas class III β‐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 β‐tubulin class III in melanoma may help identify patients with melanoma that can respond to taxanes.