Microtubule-associated protein tau (MAPT) promotes bicalutamide resistance and is associated with survival in prostate cancer

比卡鲁胺 前列腺癌 PTEN公司 张力素 雄激素受体 癌症研究 免疫组织化学 内科学 生物 τ蛋白 肿瘤科 医学 内分泌学 癌症 信号转导 阿尔茨海默病 遗传学 疾病 PI3K/AKT/mTOR通路
作者
Yohei Sekino,Xiangrui Han,Takashi Babasaki,Keisuke Goto,Shogo Inoue,Tetsutaro Hayashi,Jun Teishima,Masaki Shiota,Yukio Takeshima,Wataru Yasui,Akio Matsubara
出处
期刊:Urologic Oncology-seminars and Original Investigations [Elsevier]
卷期号:38 (10): 795.e1-795.e8 被引量:22
标识
DOI:10.1016/j.urolonc.2020.04.032
摘要

Microtubule-associated protein tau (MAPT), facilitates tubulin assembly and microtubule stabilization. Several studies have shown that overexpression of MAPT is linked to poor prognosis and is involved in taxane resistance in cancer. This study aimed to assess the expression and function of MAPT in prostate cancer (CaP). The expression of MAPT was determined using immunohistochemistry in CaP. We analyzed the interaction between MAPT, Phosphatase and Tensin Homolog (PTEN), and androgen receptor and investigated the role of MAPT in bicalutamide resistance. Immunohistochemistry in 155 CaP cases showed that 15% of them were positive for MAPT. High MAPT expression was significantly orrelated with high Gleason score and high T stage. Kaplan-Meier analysis showed that the high MAPT expression was significantly associated with poor prostate-specific antigen recurrence survival after radical prostatectomy. There was an inverse correlation between MAPT and PTEN. In the CaP cell lines, knockout of PTEN increased the expression of MAPT, whereas knockdown of MAPT suppressed the expression of androgen receptor and increased the sensitivity to bicalutamide. Furthermore, immunohistochemical staining of MAPT showed that high MAPT expression was significantly associated with poor overall survival in 74 CaP patients who were treated with androgen deprivation therapy. These results suggest that MAPT may be a promising predictive biomarker for survival and play an essential role in bicalutamide resistance in CaP.
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