Diseases of the female reproductive tract represent a significant women's health problem. Endometrial cancer is the most common gynecologic malignancy and the fourth most common cancer in women. Additionally, endometriosis affects an estimated 5 million women in the US and is commonly associated with infertility and pelvic pain. One of the major hallmarks of uterine diseases is disruption of steroid hormone control of uterine cell proliferation and differentiation. Using high density DNA microarray analysis, we have identified Mig-6 in the uterus as a target of SRC-1 and PR. Mig-6 regulates mouse fertility and the ability of P4 to attenuate E2 signaling using total and conditional ablation of Mig-6. The expression of Mig-6 in both level and cell specificity is dependent upon the menstrual cycle in the human endometrium. The expression of Mig- 6 is decreased in human endometriosis and endometrial cancer patients. The overall hypothesis of this proposal is that Mig-6 mediates the ability of P4 to inhibit endometrial cell proliferation caused by E2. The goal of this proposal will be to investigate the role of Mig-6 in the regulation of uterine endometrial function.
Specific Aim 1 will investigate the role of Mig-6 in fertility and uterine physiology by the determination of the cell type specific expression and endocrine regulation of Mig-6 in the murine uterus and the characterization of the phenotype of mice with conditional ablation of Mig-6 in the reproductive tract.
Specific Aim 2 will investigate the role of Mig-6 in the steroid regulation of uterine cell proliferation and gene expression.
Specific Aim 3 will investigate the endometrial compartment in which Mig-6 regulates endometrial steroid responsiveness by using the tissue recombination technique. The understanding of the role of Mig-6 in steroid hormone regulation, early pregnancy, proliferation, and apoptosis of the uterus will provide a strategy to develop diagnostic and therapeutic tools for infertility, endometriosis, and endometrial cancer.
The expression of Mig-6 is decreased in human endometriosis and endometrial cancer patients. The goal of this proposal will be to investigate the role of Mig-6 in the regulation of steroid hormones in uterine endometrium function. The understanding of the role of Mig-6 in steroid hormone regulation, early pregnancy, proliferation, and apoptosis of the uterus will provide a strategy to develop diagnostic and therapeutic tools for infertility, endometriosis, and endometrial cancer.
|Ahn, J I; Yoo, J-Y; Kim, T H et al. (2016) cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis. Curr Mol Med 16:276-87|
|Rubel, Cory A; Wu, San-Pin; Lin, Lin et al. (2016) A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function. Cell Rep 17:1414-1425|
|Yoo, Jung-Yoon; Kim, Tae Hoon; Kong, Sieun et al. (2016) Role of Mig-6 in hepatic glucose metabolism. J Diabetes 8:86-97|
|Fox, Chelsea; Morin, Scott; Jeong, Jae-Wook et al. (2016) Local and systemic factors and implantation: what is the evidence? Fertil Steril 105:873-84|
|Joung, Kyong Hye; Jeong, Jae-Wook; Ku, Bon Jeong (2015) The association between type 2 diabetes mellitus and women cancer: the epidemiological evidences and putative mechanisms. Biomed Res Int 2015:920618|
|Yoo, Jung-Yoon; Kim, Tae Hoon; Lee, Jae Hee et al. (2015) Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling. Biochem Biophys Res Commun 462:409-14|
|Kim, Tae Hoon; Yoo, Jung-Yoon; Wang, Zhong et al. (2015) ARID1A Is Essential for Endometrial Function during Early Pregnancy. PLoS Genet 11:e1005537|
|Kim, Byung Gak; Yoo, Jung-Yoon; Kim, Tae Hoon et al. (2015) Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis. Hum Reprod 30:1069-78|
|Kim, Tae Hoon; Yoo, Jung-Yoon; Kim, Hong Im et al. (2014) Mig-6 suppresses endometrial cancer associated with Pten deficiency and ERK activation. Cancer Res 74:7371-82|
|Pest, Michael A; Russell, Bailey A; Zhang, Yu-Wen et al. (2014) Disturbed cartilage and joint homeostasis resulting from a loss of mitogen-inducible gene 6 in a mouse model of joint dysfunction. Arthritis Rheumatol 66:2816-27|
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