Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling.
Biochem Biophys Res Commun
; 462(4): 409-14, 2015 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-25976672
ABSTRACT
Mitogen inducible gene 6 (Mig-6) is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus. Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and E2-induced endometrial cancer. To identify the molecular pathways regulated by Mig-6, we performed microarray analysis on the uterus of ovariectomized Mig-6(f/f) and PGR(cre/+)Mig-6(f/f) (Mig-6(d/d)) mice treated with vehicle or P4 for 6 h. The results revealed that 772 transcripts were significantly regulated in the Mig-6(d/d) uterus treated with vehicle as compared with Mig-6(f/f) mice. The pathway analysis showed that Mig-6 suppressed the expression of gene-related cell cycle regulation in the absence of ovarian steroid hormone. The epithelium of Mig-6(d/d) mice showed a significant increase in the number of proliferative cells compared to Mig-6(f/f) mice. This microarray analysis also revealed that 324 genes are regulated by P4 as well as Mig-6. Cited2, the developmentally important transcription factor, was identified as being regulated by the P4-Mig-6 axis. To determine the role of Cited2 in the uterus, we used the mice with Cited2 that were conditionally ablated in progesterone receptor-positive cells (PGR(cre/+)Cited2(f/f); Cited2(d/d)). Ablation of Cited2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Identification and analysis of these responsive genes will help define the role of P4 as well as Mig-6 in regulating uterine biology.
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Base de dados:
MEDLINE
Assunto principal:
Progesterona
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Transdução de Sinais
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Ciclo Celular
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Peptídeos e Proteínas de Sinalização Intracelular
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Endométrio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article