TUBB3 is associated with PTEN, neuroendocrine differentiation, and castration resistance in prostate cancer.
Aged
Benzamides
/ therapeutic use
Cell Differentiation
Humans
Male
Middle Aged
Neoplasm Metastasis
Neuroendocrine Tumors
/ pathology
Nitriles
/ therapeutic use
PTEN Phosphohydrolase
/ biosynthesis
Phenylthiohydantoin
/ therapeutic use
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Retrospective Studies
Thiohydantoins
/ therapeutic use
Tubulin
/ biosynthesis
Apalutamide
Enzalutamide
Neuroendocrine
PTEN
Prostate cancer
TUBB3
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
20
10
2020
revised:
25
02
2021
accepted:
01
03
2021
pubmed:
28
3
2021
medline:
15
12
2021
entrez:
27
3
2021
Statut:
ppublish
Résumé
Tubulin-β3 encoded by the Tubulin-β3 (TUBB3) gene is a microtubule protein. Previous studies have shown that TUBB3 expression is upregulated in castration-resistant prostate cancer (CaP) and is involved in taxane resistance. However, the biological mechanism of TUBB3 involvement in the progression to castration-resistant CaP is not fully elucidated. This study aimed to analyze the expression and function of TUBB3 in localized and metastatic CaP. TUBB3 expression was determined using immunohistochemistry in localized and metastatic CaP. We also investigated the association between TUBB3, phosphatase and tensin homolog (PTEN), and neuroendocrine differentiation and examined the involvement of TUBB3 in new antiandrogen drugs (enzalutamide and apalutamide) resistance in metastatic CaP. In 155 cases of localized CaP, immunohistochemistry showed that 5 (3.2%) of the CaP cases were positive for tubulin-β3. Kaplan-Meier analysis showed that high expression of tubulin-β3 was associated with poor prostate-specific antigen recurrence-free survival after radical prostatectomy. In 57 cases of metastatic CaP, immunohistochemistry showed that 14 (25%) cases were positive for tubulin-β3. Tubulin-β3 expression was higher in metastatic CaP than in localized CaP. High tubulin-β3 expression was correlated with negative PTEN expression. TUBB3 expression was increased in neuroendocrine CaP based on several public databases. PTEN knockout decreased the sensitivity to enzalutamide and apalutamide in 22Rv-1 cells. TUBB3 knockdown reversed the sensitivity to enzalutamide and apalutamide in PTEN-CRISPR 22Rv-1 cells. High expression of tubulin-β3 and negative expression of PTEN were significantly associated with poor overall survival in metastatic CaP treated with androgen deprivation therapy. These results suggest that TUBB3 may be a useful predictive biomarker for survival and play an essential role in antiandrogen resistance in CaP.
Sections du résumé
BACKGROUND
Tubulin-β3 encoded by the Tubulin-β3 (TUBB3) gene is a microtubule protein. Previous studies have shown that TUBB3 expression is upregulated in castration-resistant prostate cancer (CaP) and is involved in taxane resistance. However, the biological mechanism of TUBB3 involvement in the progression to castration-resistant CaP is not fully elucidated. This study aimed to analyze the expression and function of TUBB3 in localized and metastatic CaP.
METHODS
TUBB3 expression was determined using immunohistochemistry in localized and metastatic CaP. We also investigated the association between TUBB3, phosphatase and tensin homolog (PTEN), and neuroendocrine differentiation and examined the involvement of TUBB3 in new antiandrogen drugs (enzalutamide and apalutamide) resistance in metastatic CaP.
RESULTS
In 155 cases of localized CaP, immunohistochemistry showed that 5 (3.2%) of the CaP cases were positive for tubulin-β3. Kaplan-Meier analysis showed that high expression of tubulin-β3 was associated with poor prostate-specific antigen recurrence-free survival after radical prostatectomy. In 57 cases of metastatic CaP, immunohistochemistry showed that 14 (25%) cases were positive for tubulin-β3. Tubulin-β3 expression was higher in metastatic CaP than in localized CaP. High tubulin-β3 expression was correlated with negative PTEN expression. TUBB3 expression was increased in neuroendocrine CaP based on several public databases. PTEN knockout decreased the sensitivity to enzalutamide and apalutamide in 22Rv-1 cells. TUBB3 knockdown reversed the sensitivity to enzalutamide and apalutamide in PTEN-CRISPR 22Rv-1 cells. High expression of tubulin-β3 and negative expression of PTEN were significantly associated with poor overall survival in metastatic CaP treated with androgen deprivation therapy.
CONCLUSIONS
These results suggest that TUBB3 may be a useful predictive biomarker for survival and play an essential role in antiandrogen resistance in CaP.
Identifiants
pubmed: 33771409
pii: S1078-1439(21)00112-5
doi: 10.1016/j.urolonc.2021.03.001
pii:
doi:
Substances chimiques
Benzamides
0
Nitriles
0
TUBB3 protein, human
0
Thiohydantoins
0
Tubulin
0
apalutamide
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
368.e1-368.e9Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.