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


Journal

Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460

Informations de publication

Date de publication:
10 2020
Historique:
received: 09 04 2020
revised: 27 04 2020
accepted: 29 04 2020
pubmed: 21 5 2020
medline: 29 6 2021
entrez: 21 5 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32430253
pii: S1078-1439(20)30191-5
doi: 10.1016/j.urolonc.2020.04.032
pii:
doi:

Substances chimiques

AR protein, human 0
Androgen Antagonists 0
Anilides 0
Biomarkers, Tumor 0
MAPT protein, human 0
Nitriles 0
Receptors, Androgen 0
Tosyl Compounds 0
tau Proteins 0
bicalutamide A0Z3NAU9DP
PTEN Phosphohydrolase EC 3.1.3.67
PTEN protein, human EC 3.1.3.67
KLK3 protein, human EC 3.4.21.-
Kallikreins EC 3.4.21.-
Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

795.e1-795.e8

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest The authors declare no conflicts of interest.

Auteurs

Yohei Sekino (Y)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: akikosekino@gmail.com.

Xiangrui Han (X)

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

Takashi Babasaki (T)

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

Keisuke Goto (K)

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

Shogo Inoue (S)

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

Tetsutaro Hayashi (T)

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

Jun Teishima (J)

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

Masaki Shiota (M)

Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Yukio Takeshima (Y)

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

Wataru Yasui (W)

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

Akio Matsubara (A)

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

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Classifications MeSH