Oestrogens promote tumorigenesis in a mouse model for colitis-associated cancer.
Gut
; 63(2): 310-6, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-23408349
ABSTRACT
BACKGROUND:
Hormone replacement therapy increases the risk of developing ulcerative colitis in postmenopausal women. Chronic intestinal inflammation predisposes to colon cancer development, but effects of female hormones on colitis-associated cancer development have not been examined.AIM:
To investigate the role of female hormones in the dextran sodium sulfate (DSS)-azoxymethane (AOM) mouse model for colitis-associated cancer.DESIGN:
We performed ovariectomies, or sham operations, on mice, and supplemented these animals with indicated hormones. Additionally, we used oestrogen receptor α or ß (Erα or Erß) mutant mice. To study colitis or colitis-associated cancer, we used DSS only, or DSS and AOM, respectively.RESULTS:
Ovariectomy protects female mice against colitis-associated tumour development. Hormone replacement in ovariectomised mice with either oestradiol (E2), medroxyprogesterone acetate or a combination of both suggests that oestrogens are the ovary-derived factor that promotes tumour development in the context of inflammatory damage. E2-treated animals showed increased clinical symptoms and Il-6 production upon DSS-induced colitis and enhanced epithelial proliferation. Treatment with E2 markedly increased the numbers of polyps in ovariectomised mice and also strongly promoted tumour progression with all E2-treated animals developing at least one invasive adenocarcinoma, whereas, placebo-treated animals developed adenomas only. Using Er mutant mice, we find that the protumorigenic effect of oestrogen depends on both Erα and Erß.CONCLUSIONS:
Our results suggest that oestrogens promote inflammation-associated cancer development by impairing the mucosal response to inflammatory damage.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Neoplasias do Colo
/
Modelos Animais de Doenças
/
Estradiol
/
Estrogênios
/
Carcinogênese
/
Medroxiprogesterona
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Gut
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Holanda