Hexim-1 modulates androgen receptor and the TGF-ß signaling during the progression of prostate cancer.
Prostate
; 72(9): 1035-44, 2012 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-22095517
ABSTRACT
BACKGROUND:
Androgen and TGF-ß signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood.METHOD:
Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines.RESULTS:
In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-ß-dependent downstream transcription factors, such as the SMAD proteins.CONCLUSION:
Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-ß signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Fatores de Transcrição
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Transdução de Sinais
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Receptores Androgênicos
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Fator de Crescimento Transformador beta
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Progressão da Doença
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article