Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer.
Nat Cancer
; 4(5): 699-715, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-37038004
ABSTRACT
Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with 18F-fluciclovine uptake on positron emission tomography imaging. While PSMA is regulated by AR, we identified a subset of AR-negative CRPC with high PSMA. HOXB13 and AR co-occupancy at the PSMA enhancer and knockout models point to HOXB13 as an upstream regulator of PSMA in AR-positive and AR-negative prostate cancer. These data demonstrate how PSMA expression is differentially regulated across metastatic lesions and in the context of the AR, which may inform selection for PSMA-targeted therapies and development of complementary biomarkers.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata Resistentes a la Castración
Límite:
Humans
/
Male
Idioma:
En
Revista:
Nat Cancer
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos