Finally, taxane-induced cytoplasm sequestration of AR-FL was alleviated when AR-Vs were present. Through a series of deletion constructs, the microtubule-binding activity was mapped to the LBD of AR.

This could be explained, at least in part, due to the inability of taxanes to block the nuclear translocation of AR-Vs. Treatment with taxanes inhibited the transcriptional activity of AR-FL, but not those of AR-Vs. Furthermore, ectopic expression of two clinically relevant AR-Vs (AR-V7 and AR V567es), but not the full-length AR (AR-FL), reduced the sensitivities to taxanes in LNCaP cells. In taxane-resistant cell lines, we found the expression of a major variant, AR-V7, was upregulated. These variants are constitutively active and drive prostate cancer growth in a castration-resistant manner. Recently, splicing variants of AR (AR-Vs) that lack the ligand-binding domain (LBD) have been identified. Sustained signaling through the androgen receptor (AR) has been established as a hallmark of CRPC. A better understanding of the resistance mechanisms to taxane chemotherapy is both urgent and clinical significant, as taxanes (docetaxel and cabazitaxel) are being used in various clinical settings. However, half of the patients do not respond to treatment and those do respond eventually become refractory.

Received: ApAccepted: JPublished: June 22, 2015ĭocetaxel-based chemotherapy is established as a first-line treatment and standard of care for patients with metastatic castration-resistant prostate cancer. Haitao Zhang, e-mail: androgen receptor, splice variants, prostate cancer, taxane chemotherapy, microtubule ChinaĢDepartment of Pathology, Tulane University School of Medicine, New Orleans, Louisiana, USAģDepartment of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, USAĤDepartment of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USAĥDepartment of Urology, Tulane University School of Medicine, New Orleans, Louisiana, USAĦTulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana, USAħDivision of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA Guanyi Zhang 1, 2, 6, Xichun Liu 2, 6, Jianzhuo Li 1, 2, 6, Elisa Ledet 4, 5, 6, Xavier Alvarez 7, Yanfeng Qi 3, 6, Xueqi Fu 1, Oliver Sartor 4, 5, 6, Yan Dong 1, 3, 6, Haitao Zhang 2, 6ġCollege of Life Sciences, Jilin University, Changchun, P.R.

Half life 2 ar3