Oestrogen fuels the growth of endometrial hyperplastic lesions initiated by overactive Wnt/ß-catenin signalling.
Carcinogenesis
; 39(9): 1105-1116, 2018 09 21.
Article
en En
| MEDLINE
| ID: mdl-29912292
ABSTRACT
Unopposed oestrogen is responsible for approximately 80% of all the endometrial cancers. The relationship between unopposed oestrogen and endometrial cancer was indicated by the increase in the number of endometrial cancer cases due to the widespread use of oestrogen replacement therapy. Approximately 30% of the endometrial cancer patients have mutations in the Wnt signalling pathway. How the unbalanced ratios of ovarian hormones and the mutations in Wnt signalling pathway interact to cause endometrial cancer is currently unclear. To study this, we have developed a uterine epithelial cell-specific inducible cre mouse model and used 3D in vitro culture of human endometrial cancer cell lines. We showed that activating mutations in the Wnt signalling pathway for a prolonged period leads to endometrial hyperplasia but not endometrial cancer. Interestingly, unopposed oestrogen and activating mutations in Wnt signalling together drive the progression of endometrial hyperplasia to endometrial cancer. We have provided evidence that progesterone can be used as a targeted therapy against endometrial cancer cases presented with the activating mutations in Wnt signalling pathway.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Progesterona
/
Neoplasias Endometriales
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Hiperplasia Endometrial
/
Endometrio
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Estradiol
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Estrógenos
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Beta Catenina
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Vía de Señalización Wnt
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Carcinogenesis
Año:
2018
Tipo del documento:
Article