Microtubule-associated protein tau (MAPT) promotes bicalutamide resistance and is associated with survival in prostate cancer.
Aged
Androgen Antagonists
/ pharmacology
Anilides
/ pharmacology
Biomarkers, Tumor
/ analysis
Cell Line, Tumor
Chemotherapy, Adjuvant
/ methods
Disease-Free Survival
Drug Resistance, Neoplasm
/ genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Knockout Techniques
Humans
Kallikreins
/ blood
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local
/ blood
Nitriles
/ pharmacology
PTEN Phosphohydrolase
/ genetics
Prostate
/ pathology
Prostate-Specific Antigen
/ blood
Prostatectomy
Prostatic Neoplasms
/ blood
Receptors, Androgen
/ metabolism
Retrospective Studies
Tosyl Compounds
/ pharmacology
tau Proteins
/ analysis
MAPT
Prognostic marker, PTEN, Androgen receptor, Bicalutamide
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
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.e8Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest The authors declare no conflicts of interest.