Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling.
Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling.
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DOI：
10.1016/j.bbrc.2015.04.146
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发表时间：
2015-07-10
影响因子：
3.1
通讯作者：
Jeong, Jae-Wook
中科院分区：
文献类型：
--
作者：
Yoo, Jung-Yoon;Kim, Tae Hoon;Lee, Jae Hee;Dunwoodie, Sally L.;Ku, Bon Jeong;Jeong, Jae-Wook
丝裂原诱导基因6 （Mig-6）是子宫内孕酮（P4）信号抑制雌激素（E2）信号的重要介质。小鼠子宫中米格-6的消融可导致子宫内膜增生和e2诱导的子宫内膜癌。为了确定米格-6调控的分子通路，我们对卵巢切除的米格-6f/f和PGRcre/+米格-6f/f（米格-6d/d）小鼠的子宫进行了微阵列分析，这些小鼠分别给药或P4 6小时。结果显示，与米格-6f/f小鼠相比，772个转录本在载药处理的米格-6d/d子宫中被显著调节。通路分析显示，在卵巢类固醇激素缺失的情况下，Mig-6抑制基因相关细胞周期调控的表达。与米格-6f/f小鼠相比，米格-6d/d小鼠上皮细胞增殖细胞数量明显增加。微阵列分析还发现324个基因受P4和Mig-6调控。Cited2是发育重要的转录因子，经鉴定受P4-Mig-6轴调控。为了确定Cited2在子宫中的作用，我们使用了在孕激素受体阳性细胞（PGRcre/+ Cited2f/f; Cited2d/d）中有条件消融Cited2的小鼠。子宫内Cited2的消融导致子宫发生激素诱导的蜕膜反应的能力显著降低。鉴定和分析这些应答基因将有助于明确P4和Mig-6在调节子宫生物学中的作用。
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-6f/f and PGRcre/+ Mig-6f/f (Mig-6d/d) mice treated with vehicle or P4 for 6 hours. The results revealed that 772 transcripts were significantly regulated in the Mig-6d/d uterus treated with vehicle as compared with Mig-6f/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-6d/d mice showed a significant increase in the number of proliferative cells compared to Mig-6f/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 (PGRcre/+ Cited2f/f; Cited2d/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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影响因子：
11.2
作者：
Kim TH;Lee DK;Cho SN;Orvis GD;Behringer RR;Lydon JP;Ku BJ;McCampbell AS;Broaddus RR;Jeong JW
通讯作者：
Jeong JW
DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
4.8
作者：
Franco, Heather L.;Rubel, Cory A.;DeMayo, Francesco J.
通讯作者：
DeMayo, Francesco J.
DOI：
10.1111/j.1749-6632.2002.tb02765.x
发表时间：
2002-01-01
期刊：
ENDOMETRIOSIS: EMERGING RESEARCH AND INTERVENTION STRATEGIES
影响因子：
--
作者：
DeMayo, FJ;Zhao, BH;Tsai, SY
通讯作者：
Tsai, SY
影响因子：
30.8
作者：
Bamforth, SD;Bragança, J;Bhattacharya, S
通讯作者：
Bhattacharya, S