Inhibition of IGF-1R diminishes transcriptional activity of the androgen receptor and its constitutively active, C-terminally truncated counterparts Q640X and AR-V7.
World J Urol
; 34(5): 633-9, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26318637
ABSTRACT
PURPOSE:
Failure of endocrine treatment in castration-resistant prostate cancer (CRPC) is often associated with the emergence of C-terminally truncated androgen receptor variants that function as constitutively active transcription factors (i.e., AR∆LBD). The mechanisms involved in the regulation of AR∆LBD signaling are largely unknown. Since the IGF-1 pathway was repeatedly shown to affect AR function, we studied whether an inhibition of IGF-1R could also affect AR∆LBD signaling.METHODS:
Regulation of androgen receptor (AR) and AR∆LBD signaling was analyzed by reporter gene assays, immunoblotting, ELISA and quantitative RT-PCR.RESULTS:
Inhibition of IGF-1R with the small-molecule inhibitor NVP-AEW541 reduced the transcriptional activity of the AR and its truncated counterparts Q640X and AR-V7. As shown in Q640X, the inhibition of transcriptional activity was paralleled by a decreased receptor phosphorylation.CONCLUSIONS:
Inhibition of IGF-1R leads to a down-regulation of AR∆LBD signaling and provides a rationale for CRPC therapies targeting growth factor receptors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Transdução de Sinais
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Receptores Androgênicos
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Neoplasias de Próstata Resistentes à Castração
Limite:
Humans
/
Male
Idioma:
En
Revista:
World J Urol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha