Portal de investigação
Novel Insights on the Role of Epigenetics in Androgen Receptor's Expression in Prostate Cancer
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Camilo, V
- Pacheco, MB
- Moreira-Silva, F
- Outeiro-Pinho, G
- Gaspar, VM
- Mano, JF
- Henrique, R
- Jerónimo, C
Unidades de investigação
Abstract
The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5 ' UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.
Dados da publicação
- ISSN/ISSNe:
- 2218-273X, 2218-273X
- Tipo:
- Article
- Páginas:
- 1526-
- DOI:
- 10.3390/biom13101526
- Link para outro recurso:
- www.scopus.com
Biomolecules Multidisciplinary Digital Publishing Institute (MDPI)
Documentos
- Não há documentos
Filiações
Keywords
- prostate cancer; androgen receptor; DNA methylation; epigenetics; transcriptional repression
Financiamento
Proyectos asociados
Epigenetic and transcriptional analysis ofTSC2 in leukocyte DNA from tuberous sclerosis patients.
Investigador Principal: Cristina Joana Moreira Marques
Estudo Observacional Académico (Epigenetic TSA) . Tuberous Sclerosis Association . 2019
Citar a publicação
Camilo V,Pacheco MB,Moreira F,Outeiro G,Gaspar VM,Mano JF,Marques J,Henrique R,Jerónimo C. Novel Insights on the Role of Epigenetics in Androgen Receptor's Expression in Prostate Cancer. Biomolecules. 2023. 13. (10):p. 1526-1526. IF:5,500. (1).
