微管相关蛋白 tau（MAPT）促进比卡鲁胺耐药，并与前列腺癌患者的生存相关。

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

机构信息

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

Urol Oncol. 2020 Oct;38(10):795.e1-795.e8. doi: 10.1016/j.urolonc.2020.04.032. Epub 2020 May 17.

DOI:10.1016/j.urolonc.2020.04.032

PMID:32430253

Abstract

INTRODUCTION

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).

METHODS

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.

RESULTS

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.

CONCLUSION

These results suggest that MAPT may be a promising predictive biomarker for survival and play an essential role in bicalutamide resistance in CaP.

摘要

简介

微管相关蛋白 tau（MAPT）促进微管蛋白组装和微管稳定。多项研究表明，MAPT 的过表达与预后不良有关，并与癌症中的紫杉烷耐药有关。本研究旨在评估 MAPT 在前列腺癌（CaP）中的表达和功能。

方法

使用免疫组织化学方法检测 CaP 中 MAPT 的表达。我们分析了 MAPT 与磷酸酶和张力蛋白同源物（PTEN）和雄激素受体之间的相互作用，并研究了 MAPT 在比卡鲁胺耐药中的作用。

结果

对 155 例 CaP 病例的免疫组化分析显示，其中 15%的病例 MAPT 阳性。高 MAPT 表达与高 Gleason 评分和高 T 分期显著相关。Kaplan-Meier 分析显示，高 MAPT 表达与根治性前列腺切除术后前列腺特异性抗原复发生存不良显著相关。MAPT 与 PTEN 呈负相关。在 CaP 细胞系中，敲除 PTEN 会增加 MAPT 的表达，而敲低 MAPT 会抑制雄激素受体的表达并增加对比卡鲁胺的敏感性。此外，MAPT 的免疫组织化学染色显示，在接受雄激素剥夺治疗的 74 例 CaP 患者中，高 MAPT 表达与总体生存不良显著相关。