{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:46Z","timestamp":1784557126118,"version":"3.55.0"},"reference-count":52,"publisher":"Bioscientifica","issue":"11","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>\n                    Cushing\u2019s syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing\u2019s syndrome). Hypercortisolemic features of ectopic Cushing\u2019s syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing\u2019s syndrome. We show that ectopic\n                    <jats:italic>hPOMC<\/jats:italic>\n                    transcription proceeds independently of pituitary-specific Tpit\/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating\n                    <jats:italic>hPOMC<\/jats:italic>\n                    . We identify an E2F1 cluster binding to the proximal\n                    <jats:italic>hPOMC<\/jats:italic>\n                    promoter region (\u221242 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337.\n                    <jats:italic>hPOMC<\/jats:italic>\n                    mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed\n                    <jats:italic>hPOMC<\/jats:italic>\n                    gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing\u2019s cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated\n                    <jats:italic>hPOMC<\/jats:italic>\n                    transcription is a potential target for suppressing ACTH production in ectopic Cushing\u2019s syndrome.\n                  <\/jats:p>","DOI":"10.1530\/erc-16-0206","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T21:40:42Z","timestamp":1475876442000},"page":"857-870","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":30,"title":["E2F1-mediated human POMC expression in ectopic Cushing\u2019s syndrome"],"prefix":"10.1530","volume":"23","author":[{"given":"Takako","family":"Araki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Ai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Tone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cuevas-Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Heltsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Tone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Melmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016100718401908000_23.11.857.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-001-0032-5"},{"key":"2016100718401908000_23.11.857.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7924"},{"key":"2016100718401908000_23.11.857.3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11182"},{"key":"2016100718401908000_23.11.857.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)84800-X"},{"key":"2016100718401908000_23.11.857.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310589110"},{"key":"2016100718401908000_23.11.857.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.106"},{"key":"2016100718401908000_23.11.857.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105743"},{"key":"2016100718401908000_23.11.857.8","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(85)80078-8"},{"key":"2016100718401908000_23.11.857.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306182110"},{"key":"2016100718401908000_23.11.857.10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204242"},{"key":"2016100718401908000_23.11.857.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(94)90522-3"},{"key":"2016100718401908000_23.11.857.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3350"},{"key":"2016100718401908000_23.11.857.13","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s11102-015-0692-z","article-title":"Osilodrostat, a potent oral 11beta-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing\u2019s disease","volume":"19","author":"Fleseriu","year":"2015","journal-title":"Pituitary"},{"key":"2016100718401908000_23.11.857.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.8998"},{"key":"2016100718401908000_23.11.857.15","doi-asserted-by":"publisher","DOI":"10.1038\/362083a0"},{"key":"2016100718401908000_23.11.857.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6933"},{"key":"2016100718401908000_23.11.857.17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2527"},{"key":"2016100718401908000_23.11.857.18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1542"},{"key":"2016100718401908000_23.11.857.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313063200"},{"key":"2016100718401908000_23.11.857.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096357"},{"key":"2016100718401908000_23.11.857.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00282-3"},{"key":"2016100718401908000_23.11.857.22","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.10.1284"},{"key":"2016100718401908000_23.11.857.23","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0422"},{"key":"2016100718401908000_23.11.857.24","first-page":"5915","article-title":"Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells","volume":"43","author":"Lechner","year":"1983","journal-title":"Cancer Research"},{"key":"2016100718401908000_23.11.857.25","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.4.1668"},{"key":"2016100718401908000_23.11.857.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141234898"},{"key":"2016100718401908000_23.11.857.27","doi-asserted-by":"crossref","first-page":"2557\u20132564","DOI":"10.1210\/jc.2015-1606","article-title":"Cyclin E \u2013 mediated human proopiomelanocortin regulation as a therapeutic target for Cushing disease","volume":"100","author":"Liu","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2016100718401908000_23.11.857.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018091108"},{"key":"2016100718401908000_23.11.857.29","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0121"},{"key":"2016100718401908000_23.11.857.30","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.11.7549"},{"key":"2016100718401908000_23.11.857.31","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1770365"},{"key":"2016100718401908000_23.11.857.32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1622"},{"key":"2016100718401908000_23.11.857.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68699-6"},{"key":"2016100718401908000_23.11.857.34","doi-asserted-by":"publisher","DOI":"10.1210\/me.15.2.338"},{"key":"2016100718401908000_23.11.857.35","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1818"},{"key":"2016100718401908000_23.11.857.36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301892"},{"key":"2016100718401908000_23.11.857.37","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19800301)45:5<906::AID-CNCR2820450513>3.0.CO;2-H"},{"key":"2016100718401908000_23.11.857.38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202635"},{"key":"2016100718401908000_23.11.857.39","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0150187"},{"key":"2016100718401908000_23.11.857.40","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.11.6673"},{"key":"2016100718401908000_23.11.857.41","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0274"},{"key":"2016100718401908000_23.11.857.42","first-page":"4914","article-title":"Cell lines from human colon carcinoma with unusual cell products, double minutes, and homogeneously staining regions","volume":"39","author":"Quinn","year":"1979","journal-title":"Cancer Research"},{"key":"2016100718401908000_23.11.857.43","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.282871"},{"key":"2016100718401908000_23.11.857.44","first-page":"3276","article-title":"Glucocorticoid receptor structure and function in glucocorticoid-resistant small cell lung carcinoma cells","volume":"56","author":"Ray","year":"1996","journal-title":"Cancer Research"},{"key":"2016100718401908000_23.11.857.45","doi-asserted-by":"publisher","DOI":"10.1038\/77124"},{"key":"2016100718401908000_23.11.857.46","first-page":"63","article-title":"ACTH: cellular peptide hormone synthesis and secretory pathways","volume":"50","author":"Stevens","year":"2010","journal-title":"Results and Problems in Cell Differentiation"},{"key":"2016100718401908000_23.11.857.47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/11.19.6847"},{"key":"2016100718401908000_23.11.857.48","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.12.6994"},{"key":"2016100718401908000_23.11.857.49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.1.286"},{"key":"2016100718401908000_23.11.857.50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109889200"},{"key":"2016100718401908000_23.11.857.51","doi-asserted-by":"publisher","DOI":"10.1038\/ni1549"},{"key":"2016100718401908000_23.11.857.52","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0030065"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/23\/11\/857.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/23\/11\/857.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:45Z","timestamp":1784555625000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/23\/11\/857-870\/34026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11]]},"references-count":52,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.1530\/erc-16-0206","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11]]}}}