Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemoresistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals.
Oncogene
; 35(47): 6065-6076, 2016 11 24.
Article
en En
| MEDLINE
| ID: mdl-27375022
ABSTRACT
Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) and are associated with PCa progression. As the current androgen deprivation therapy with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here, we found NEPCa cells could increase the docetaxel resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed that NEPCa could increase the docetaxel resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or shPTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Transducción de Señal
/
Receptores Androgénicos
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Carcinoma Neuroendocrino
/
Resistencia a Antineoplásicos
/
Receptor de Hormona Paratiroídea Tipo 1
/
Proteínas Quinasas p38 Activadas por Mitógenos
/
Proteínas de Choque Térmico HSP27
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2016
Tipo del documento:
Article
País de afiliación:
China