Chemical castration and anti-androgens induce differential gene expression in prostate cancer.
J Pathol
; 227(3): 336-45, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22431170
ABSTRACT
Endocrine therapy by castration or anti-androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti-androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein-coding genes. An in silico Bayesian modelling tool was used to assess cancer-specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two-fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen-regulated genes, according to re-analysis of previous data on gene expression, androgen receptor-binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2-ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion-negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one-half of these genes and thus diminished the differences between the fusion-positive and -negative samples. This study reports the significantly different effects of an anti-androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2-ERG fusion seems to bring many proliferation-related genes under androgen regulation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Compostos de Tosil
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Castração
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Regulação Neoplásica da Expressão Gênica
/
Gosserrelina
/
Antineoplásicos Hormonais
/
Antagonistas de Androgênios
/
Anilidas
/
Neoplasias Hormônio-Dependentes
/
Nitrilas
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Pathol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Finlândia