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

Yohei Sekino, Xiangrui Han, Takashi Babasaki, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Jun Teishima, Masaki Shiota, Yukio Takeshima, Wataru Yasui, Akio Matsubara

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)795.e1-795.e8
JournalUrologic Oncology: Seminars and Original Investigations
Volume38
Issue number10
DOIs
Publication statusAccepted/In press - Jan 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

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    Sekino, Y., Han, X., Babasaki, T., Goto, K., Inoue, S., Hayashi, T., Teishima, J., Shiota, M., Takeshima, Y., Yasui, W., & Matsubara, A. (Accepted/In press). Microtubule-associated protein tau (MAPT) promotes bicalutamide resistance and is associated with survival in prostate cancer. Urologic Oncology: Seminars and Original Investigations, 38(10), 795.e1-795.e8. https://doi.org/10.1016/j.urolonc.2020.04.032