YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.
Mol Med Rep
; 12(4): 4867-76, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26126522
Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to lifethreatening androgenresistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcriptionquantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with paraPCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumournodemetastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cellcycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
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Hiperplasia Prostática
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Regulación Neoplásica de la Expresión Génica
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Apoptosis
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Proteínas Adaptadoras Transductoras de Señales
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Proliferación Celular
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Neoplasias de la Próstata Resistentes a la Castración
Tipo de estudio:
Diagnostic_studies
Límite:
Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article