{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:12Z","timestamp":1787028492639,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["P50CA09825"],"award-info":[{"award-number":["P50CA09825"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Women with complex atypical hyperplasia (CAH) or early-stage endometrioid endometrial cancer (EEC) are candidates for fertility preservation. The most common approach is progesterone (P4) therapy and deferral of hysterectomy until after completion of childbearing. However, P4 therapy response rates vary, and molecular mechanisms behind P4 resistance are poorly understood. One potential molecular cause of P4 resistance is a loss or attenuation of PGR expression. Mitogen-inducible gene 6 (MIG-6) is critical for P4 responsiveness. MIG-6 protein expression in the endometrial epithelial and stromal cells from women with CAH and EEC was significantly lower compared to women without CAH or EEC. The P4-responsive women (10\/15) exhibited an increase of MIG-6 expression in epithelial and stromal cells compared to P4-resistant women (5\/15). In addition, immunohistochemical analysis for PGR results showed that stromal PGR levels are significantly higher in P4-responsive women compared to P4-resistant women, whereas epithelial PGR expression was not different. A reverse correlation of MIG-6 and pAKT levels was observed in early-stage EEC patients. Studies strongly suggest that loss of MIG-6 and PGR and activation of pAKT lead to P4 resistance in CAH and EEC. These results will help to elucidate the molecular mechanism leading to P4 resistance in CAH and EEC.<\/jats:p>","DOI":"10.3390\/ijms232314596","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T09:50:52Z","timestamp":1669197052000},"page":"14596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["MIG-6 Is Critical for Progesterone Responsiveness in Human Complex Atypical Hyperplasia and Early-Stage Endometrial Cancer"],"prefix":"10.3390","volume":"23","author":[{"given":"Olivia","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Public Health Sciences Program, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell R.","family":"Broaddus","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Lessey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Atrium Health Wake Forest Baptist, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John I.","family":"Risinger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women\u2019s Health, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"},{"name":"Department of Obstetrics, Gynecology and Women\u2019s Health, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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