TY - JOUR
T1 - Microtubule-associated protein tau (MAPT) promotes bicalutamide resistance and is associated with survival in prostate cancer
AU - Sekino, Yohei
AU - Han, Xiangrui
AU - Babasaki, Takashi
AU - Goto, Keisuke
AU - Inoue, Shogo
AU - Hayashi, Tetsutaro
AU - Teishima, Jun
AU - Shiota, Masaki
AU - Takeshima, Yukio
AU - Yasui, Wataru
AU - Matsubara, Akio
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.urolonc.2020.04.032
DO - 10.1016/j.urolonc.2020.04.032
M3 - Article
C2 - 32430253
AN - SCOPUS:85084587505
SN - 1078-1439
VL - 38
SP - 795.e1-795.e8
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 10
ER -
