Decreased RARß expression induces abundant inflammation and cervical precancerous lesions.
Exp Cell Res
; 346(1): 40-52, 2016 08 01.
Article
em En
| MEDLINE
| ID: mdl-27207583
ABSTRACT
It is well known that vitamin A and its receptors protect against cancer development and that Retinoid Acid Receptor ß (RARß) is epigenetically silenced during tumoral progression. Cervical Cancer (CC) has been causally linked to high risk human papillomavirus (HR-HPV) infection. However, host factors are important in determining the outcome of persistent HR-HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Increasing evidence suggests that low diet in vitamin A and their receptors participate in the development of CC. The aim of this study has been to investigate the effects of abated RARß expression in the development of cervical premalignant lesions in 4 month-old conditional mice (RARß(L-/L-)). Results demonstrated the development of spontaneous squamous metaplasia, inflammatory infiltrate, enhanced mitotic activity, loss of cell differentiation, as well as decreased apoptosis and p16(INK4a) protein levels in RARß(L-/L-) mice cervix. All these changes are hallmarks of moderate dysplasia. Importantly, our results suggest that the low expression of RARß, may induce the down regulation of p16(INK4a), chronic inflammation and decreased apoptosis and may be involved in vulnerability to HR-HPV and early stage cervical carcinogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Lesões Pré-Cancerosas
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Neoplasias do Colo do Útero
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Receptores do Ácido Retinoico
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Inflamação
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article