{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:05:45Z","timestamp":1780344345117,"version":"3.54.1"},"reference-count":47,"publisher":"The Endocrine Society","issue":"2","funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1081461"],"award-info":[{"award-number":["APP1081461"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John Hunter Hospital Charitable Trust"},{"DOI":"10.13039\/501100001171","name":"Cancer Institute New South Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bulk-type symptoms. Despite this, very little is known about patterns of ECM protein expression in fibroids and whether these are influenced by the most common genetic anomalies, which relate to MED12. We performed extensive genetic and proteomic analyses of clinically annotated fibroids and adjacent normal myometrium to identify the composition and expression patterns of ECM proteins in MED12 mutation\u2013positive and mutation\u2013negative uterine fibroids. Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged\u2013based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated (&amp;gt;1.5-fold) and downregulated (&amp;lt;0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.<\/jats:p>","DOI":"10.1210\/en.2017-03018","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T19:04:16Z","timestamp":1513191856000},"page":"1106-1118","source":"Crossref","is-referenced-by-count":25,"title":["Proteomic Profiling of Human Uterine Fibroids Reveals Upregulation of the Extracellular Matrix Protein Periostin"],"prefix":"10.1210","volume":"159","author":[{"given":"M Fairuz B","family":"Jamaluddin","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-An","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazmin","family":"Brown","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preety","family":"Bajwa","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathima B","family":"Nagendra","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Skerrett-Byrne","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Hondermarck","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Baker","sequence":"additional","affiliation":[{"name":"School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt D","family":"Dun","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney J","family":"Scott","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravin","family":"Nahar","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"},{"name":"Department of Maternity and Gynaecology, John Hunter Hospital, New Lambton Heights, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep S","family":"Tanwar","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"issue":"4","key":"2020071623142139100_B1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/ajcp\/94.4.435","article-title":"The frequency of uterine leiomyomas","volume":"94","author":"Cramer","year":"1990","journal-title":"Am J Clin Pathol"},{"issue":"1","key":"2020071623142139100_B2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1067\/mob.2003.99","article-title":"High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence","volume":"188","author":"Baird","year":"2003","journal-title":"Am J Obstet Gynecol"},{"issue":"4","key":"2020071623142139100_B3","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/humrep\/deh698","article-title":"Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review","volume":"20","author":"Arslan","year":"2005","journal-title":"Hum Reprod"},{"issue":"14","key":"2020071623142139100_B4","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1056\/NEJMra1209993","article-title":"Uterine fibroids","volume":"369","author":"Bulun","year":"2013","journal-title":"N Engl J Med"},{"key":"2020071623142139100_B5","doi-asserted-by":"crossref","first-page":"16043","DOI":"10.1038\/nrdp.2016.43","article-title":"Uterine fibroids","volume":"2","author":"Stewart","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2020071623142139100_B6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1056\/NEJMoa1302736","article-title":"Characterization of uterine leiomyomas by whole-genome sequencing","volume":"369","author":"Mehine","year":"2013","journal-title":"N Engl J Med"},{"issue":"5","key":"2020071623142139100_B7","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1073\/pnas.1518752113","article-title":"Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers","volume":"113","author":"Mehine","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6053","key":"2020071623142139100_B8","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1126\/science.1208930","article-title":"MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas","volume":"334","author":"M\u00e4kinen","year":"2011","journal-title":"Science"},{"issue":"9","key":"2020071623142139100_B9","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/humu.22612","article-title":"Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas","volume":"35","author":"K\u00e4mpj\u00e4rvi","year":"2014","journal-title":"Hum Mutat"},{"issue":"6","key":"2020071623142139100_B10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.tibs.2010.02.004","article-title":"The human Mediator complex: a versatile, genome-wide regulator of transcription","volume":"35","author":"Taatjes","year":"2010","journal-title":"Trends Biochem Sci"},{"issue":"12","key":"2020071623142139100_B11","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/bjc.2016.130","article-title":"MED12 mutations and FH inactivation are mutually exclusive in uterine leiomyomas","volume":"114","author":"K\u00e4mpj\u00e4rvi","year":"2016","journal-title":"Br J Cancer"},{"issue":"8","key":"2020071623142139100_B12","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1172\/JCI81534","article-title":"Med12 gain-of-function mutation causes leiomyomas and genomic instability","volume":"125","author":"Mittal","year":"2015","journal-title":"J Clin Invest"},{"issue":"1","key":"2020071623142139100_B13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humupd\/dmu048","article-title":"Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications","volume":"21","author":"Moravek","year":"2015","journal-title":"Hum Reprod Update"},{"issue":"50","key":"2020071623142139100_B14","doi-asserted-by":"crossref","first-page":"19887","DOI":"10.1073\/pnas.0808188105","article-title":"Growth of uterine leiomyomata among premenopausal black and white women","volume":"105","author":"Peddada","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"2020071623142139100_B15","first-page":"36","article-title":"Reassessing hysterectomy","volume":"95","author":"Stewart","year":"2012","journal-title":"Minn Med"},{"issue":"9","key":"2020071623142139100_B16","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1242\/dev.024166","article-title":"Mechanical control of tissue and organ development","volume":"137","author":"Mammoto","year":"2010","journal-title":"Development"},{"issue":"12","key":"2020071623142139100_B17","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"12","key":"2020071623142139100_B18","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embr.201439246","article-title":"The extracellular matrix modulates the hallmarks of cancer","volume":"15","author":"Pickup","year":"2014","journal-title":"EMBO Rep"},{"issue":"3","key":"2020071623142139100_B19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1055\/s-0030-1251475","article-title":"Why leiomyomas are called fibroids: the central role of extracellular matrix in symptomatic women","volume":"28","author":"Malik","year":"2010","journal-title":"Semin Reprod Med"},{"issue":"9","key":"2020071623142139100_B20","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1074\/mcp.M114.046110","article-title":"Proteotranscriptomic profiling of 231-BR breast cancer cells: identification of potential biomarkers and therapeutic targets for brain metastasis","volume":"14","author":"Dun","year":"2015","journal-title":"Mol Cell Proteomics"},{"issue":"5","key":"2020071623142139100_B21","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.18632\/oncotarget.13919","article-title":"Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice","volume":"8","author":"Bajwa","year":"2017","journal-title":"Oncotarget"},{"key":"2020071623142139100_B22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc B"},{"issue":"7","key":"2020071623142139100_B23","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ijc.27424","article-title":"MED12 mutations in uterine fibroids--their relationship to cytogenetic subgroups","volume":"131","author":"Markowski","year":"2012","journal-title":"Int J Cancer"},{"issue":"3","key":"2020071623142139100_B24","doi-asserted-by":"crossref","first-page":"e33251","DOI":"10.1371\/journal.pone.0033251","article-title":"Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas","volume":"7","author":"McGuire","year":"2012","journal-title":"PLoS One"},{"issue":"3","key":"2020071623142139100_B25","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.celrep.2014.03.047","article-title":"Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity","volume":"7","author":"Turunen","year":"2014","journal-title":"Cell Reports"},{"issue":"3","key":"2020071623142139100_B26","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.18632\/oncotarget.2753","article-title":"Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia","volume":"6","author":"K\u00e4mpj\u00e4rvi","year":"2015","journal-title":"Oncotarget"},{"issue":"23","key":"2020071623142139100_B27","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1007\/s00018-017-2643-5","article-title":"Introductory review: periostin-gene and protein structure","volume":"74","author":"Kudo","year":"2017","journal-title":"Cell Mol Life Sci"},{"issue":"7","key":"2020071623142139100_B28","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1359\/jbmr.1999.14.7.1239","article-title":"Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta","volume":"14","author":"Horiuchi","year":"1999","journal-title":"J Bone Min Res"},{"issue":"19","key":"2020071623142139100_B29","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1007\/s00018-011-0784-5","article-title":"Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell","volume":"68","author":"Kudo","year":"2011","journal-title":"Cell Mol Life Sci"},{"issue":"3","key":"2020071623142139100_B30","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/prep.1995.1040","article-title":"Expression and characterization of murine osteoblast-specific factor 2 (OSF-2) in a baculovirus expression system","volume":"6","author":"Sugiura","year":"1995","journal-title":"Protein Expr Purif"},{"issue":"3","key":"2020071623142139100_B31","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1074\/jbc.M109.051961","article-title":"Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture","volume":"285","author":"Kii","year":"2010","journal-title":"J Biol Chem"},{"issue":"17","key":"2020071623142139100_B32","doi-asserted-by":"crossref","first-page":"13294","DOI":"10.1074\/jbc.M109.088864","article-title":"Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase","volume":"285","author":"Maruhashi","year":"2010","journal-title":"J Biol Chem"},{"issue":"7","key":"2020071623142139100_B33","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCRESAHA.107.159517","article-title":"Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart","volume":"102","author":"Snider","year":"2008","journal-title":"Circ Res"},{"issue":"23","key":"2020071623142139100_B34","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1007\/s00018-017-2644-4","article-title":"Periostin and its interacting proteins in the construction of extracellular architectures","volume":"74","author":"Kii","year":"2017","journal-title":"Cell Mol Life Sci"},{"issue":"10","key":"2020071623142139100_B35","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/hed.20253","article-title":"Differential expression of osteoblast-specific factor 2 and polymeric immunoglobulin receptor genes in nasopharyngeal carcinoma","volume":"27","author":"Chang","year":"2005","journal-title":"Head Neck"},{"issue":"14","key":"2020071623142139100_B36","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.1158\/0008-5472.CAN-05-4540","article-title":"Periostin promotes invasion and anchorage-independent growth in the metastatic process of head and neck cancer","volume":"66","author":"Kudo","year":"2006","journal-title":"Cancer Res"},{"issue":"10","key":"2020071623142139100_B37","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/sj.bjc.6603431","article-title":"Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer","volume":"95","author":"Siriwardena","year":"2006","journal-title":"Br J Cancer"},{"issue":"2","key":"2020071623142139100_B38","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.canlet.2009.02.030","article-title":"Upregulated expression of periostin by hypoxia in non-small-cell lung cancer cells promotes cell survival via the Akt\/PKB pathway","volume":"281","author":"Ouyang","year":"2009","journal-title":"Cancer Lett"},{"issue":"9","key":"2020071623142139100_B39","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1128\/MCB.24.9.3992-4003.2004","article-title":"Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression","volume":"24","author":"Shao","year":"2004","journal-title":"Mol Cell Biol"},{"issue":"23","key":"2020071623142139100_B40","first-page":"6744","article-title":"Differential gene expression between normal and tumor-derived ovarian epithelial cells","volume":"60","author":"Ismail","year":"2000","journal-title":"Cancer Res"},{"issue":"4","key":"2020071623142139100_B41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1535-6108(04)00081-9","article-title":"Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt\/PKB pathway","volume":"5","author":"Bao","year":"2004","journal-title":"Cancer Cell"},{"issue":"14","key":"2020071623142139100_B42","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/sj.onc.1210009","article-title":"Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the beta4 integrin and the PI3k pathway","volume":"26","author":"Baril","year":"2007","journal-title":"Oncogene"},{"issue":"10","key":"2020071623142139100_B43","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.ejso.2013.06.023","article-title":"High preoparative levels of serum periostin are associated with poor prognosis in patients with hepatocellular carcinoma after hepatectomy","volume":"39","author":"Lv","year":"2013","journal-title":"Eur J Surg Oncol"},{"issue":"1","key":"2020071623142139100_B44","doi-asserted-by":"crossref","first-page":"385.","DOI":"10.1007\/s12032-012-0385-7","article-title":"High-level expression of periostin is closely related to metastatic potential and poor prognosis of hepatocellular carcinoma","volume":"30","author":"Lv","year":"2013","journal-title":"Med Oncol"},{"key":"2020071623142139100_B45","first-page":"5358","article-title":"Periostin Secreted by Epithelial Ovarian Carcinoma Is a Ligand for \u03b1V\u03b23 and \u03b1V\u03b25 integrins and promotes cell motility","volume":"62","author":"Gillan","year":"2002","journal-title":"Cancer Res"},{"issue":"3","key":"2020071623142139100_B46","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3892\/ijo.2012.1530","article-title":"Periostin activates integrin \u03b15\u03b21 through a PI3K\/AKT\u2011dependent pathway in invasion of cholangiocarcinoma","volume":"41","author":"Utispan","year":"2012","journal-title":"Int J Oncol"},{"issue":"27","key":"2020071623142139100_B47","doi-asserted-by":"crossref","first-page":"10978","DOI":"10.1073\/pnas.1204708109","article-title":"Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-\u03b2 pathway","volume":"109","author":"Lorts","year":"2012","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/159\/2\/1106\/23727939\/en.2017-03018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/159\/2\/1106\/23727939\/en.2017-03018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T18:08:44Z","timestamp":1719684524000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/159\/2\/1106\/4736307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,13]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2017-03018","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,2]]},"published":{"date-parts":[[2017,12,13]]}}}