{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:47:48Z","timestamp":1789980468852,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T00:00:00Z","timestamp":1534723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HD57877"],"award-info":[{"award-number":["P01HD57877"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uterine leiomyomas (ULM) are histologically and molecularly heterogeneous and clinically they grow at vastly different rates. Several driver gene mutations have been identified in ULM, including <jats:italic>MED12<\/jats:italic> mutations, <jats:italic>HMGA2<\/jats:italic> overexpression, and biallelic FH inactivation. ULM with different driver mutant genes may use different molecular pathways, but currently no clear correlation between gene mutations and growth related pathways has been established. To better define this relationship, we collected ULM with <jats:italic>MED12<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u200925), <jats:italic>HMGA2<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u200915), and <jats:italic>FH<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u200927) mutations and examined the sex steroid hormone, cell cycle, and AKT pathway genes by immunohistochemistry. While ER and PR were highly expressed in all types of ULM, <jats:italic>FH<\/jats:italic> ULM showed lower <jats:italic>ER<\/jats:italic> expression and higher <jats:italic>PR<\/jats:italic> expression. <jats:italic>HMGA2<\/jats:italic> tumors had significantly higher levels of AKT signaling and mitogenic activity than other ULM types. <jats:italic>HMGA2<\/jats:italic> activated AKT signaling through upregulation of IGF2BP2. Silencing <jats:italic>HMGA2<\/jats:italic> in ULM cells resulted in downregulation of AKT and upregulation of p16 and p21, which eventually led to cell senescence. <jats:italic>HMGA2<\/jats:italic> overexpression in ULM is not only related to tumor development but also plays a role in controlling cellular proliferation through the AKT pathway.<\/jats:p>","DOI":"10.1002\/gcc.22643","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T08:54:51Z","timestamp":1527065691000},"page":"485-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Comparative analysis of <i>AKT<\/i> and the related biomarkers in uterine leiomyomas with <i>MED12, HMGA2<\/i>, and <i>FH<\/i> mutations"],"prefix":"10.1002","volume":"57","author":[{"given":"Jia","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne","family":"Ubango","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debabrata","family":"Chakravarti","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Julie","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-2793","authenticated-orcid":false,"given":"Jian\u2010Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Feinberg School of Medicine Northwestern University  Chicago Illinois"},{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine Northwestern University  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-200202000-00012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.99"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808188105"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0672-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518752113"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.243"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.130"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00283-X"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20415"},{"key":"e_1_2_6_11_1","first-page":"351","article-title":"Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15","volume":"15","author":"Quade BJ","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.36"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2550"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208930"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00993-08"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1744"},{"key":"e_1_2_6_17_1","article-title":"Fumarate hydratase mutations and alterations in leiomyoma with bizarre nuclei","volume":"1","author":"Zhang Q","year":"2017","journal-title":"Int J Gynecol Pathol"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000703"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02699.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.12.116"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603283"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2093"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1601132"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","unstructured":"WuJ WeiJJ. 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