Melanoma cell sensitivity to Docetaxel-induced apoptosis is determined by class III beta-tubulin levels.
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.
Mhaidat
Nizar M
NM
Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Thorne
Rick F
RF
de Bock
Charles Edo
CE
Zhang
Xu Dong
XD
Hersey
Peter
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D043823:Taxoids / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel