title: Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling.
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.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI, United States.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI, United States.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI, United States.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School and the School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales 2033, Australia.
authors.forename: Sally L
authors.initials: SL
authors.lastname: Dunwoodie
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea. Electronic address: bonjeong@cnu.ac.kr.
authors.forename: Bon Jeong
authors.initials: BJ
authors.lastname: Ku
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI, United States; Department of Women's Health, Spectrum Health System, Grand Rapids, MI, United States. Electronic address: JaeWook.Jeong@hc.msu.edu.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010052:Ovariectomy; D011374:Progesterone / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C475819:Errfi1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011374:Progesterone
keywords: Cited2; Mig-6; Progesterone; Uterus