Novel Insights on the Role of Epigenetics in Androgen Receptor's Expression in Prostate Cancer

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Camilo, V (Autor) Outra; Pacheco, MB (Autor) Outra; Moreira-Silva, F (Autor) Outra; Outeiro-Pinho, G (Autor) Outra; Gaspar, VM (Autor) Outra; Mano, JF (Autor) Outra; Marques, CJ (Autor) FMUP; Henrique, R (Autor) Outra; Jerónimo, C (Autor) Outra

Revista

Título: Biomolecules

Vol. 13

Página Final: 1526

ISSN: 2218-273X

Editora: MDPI

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-00Z-8WN

DOI: 10.3390/biom13101526

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16