{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:18:02Z","timestamp":1773829082138,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Campania POR","award":["FESR 2014-2020 \"SATIN\""],"award-info":[{"award-number":["FESR 2014-2020 \"SATIN\""]}]},{"name":"Italian Ministry of University and Research (MIUR)","award":["PON03PE_00060_7"],"award-info":[{"award-number":["PON03PE_00060_7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The transcription factor Forkhead box E1 (FOXE1) is a key player in thyroid development and function and has been identified by genome-wide association studies as a susceptibility gene for papillary thyroid cancer. Several cancer-associated polymorphisms fall into gene regulatory regions and are likely to affect FOXE1 expression levels. However, the possibility that changes in FOXE1 expression modulate thyroid cancer development has not been investigated. Here, we describe the effects of FOXE1 gene dosage reduction on cancer phenotype in vivo. Mice heterozygous for FOXE1 null allele (FOXE1+\/\u2212) were crossed with a BRAFV600E-inducible cancer model to develop thyroid cancer in either a FOXE1+\/+ or FOXE1+\/\u2212 genetic background. In FOXE1+\/+ mice, cancer histological features are quite similar to that of human high-grade papillary thyroid carcinomas, while cancers developed with reduced FOXE1 gene dosage maintain morphological features resembling less malignant thyroid cancers, showing reduced proliferation index and increased apoptosis as well. Such cancers, however, appear severely undifferentiated, indicating that FOXE1 levels affect thyroid differentiation during neoplastic transformation. These results show that FOXE1 dosage exerts pleiotropic effects on thyroid cancer phenotype by affecting histology and regulating key markers of tumor differentiation and progression, thus suggesting the possibility that FOXE1 could behave as lineage-specific oncogene in follicular cell-derived thyroid cancer.<\/jats:p>","DOI":"10.3390\/ijms22010025","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:39:29Z","timestamp":1608669569000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["FOXE1 Gene Dosage Affects Thyroid Cancer Histology and Differentiation In Vivo"],"prefix":"10.3390","volume":"22","author":[{"given":"Sara C.","family":"Credendino","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"},{"name":"Institute of Experimental Endocrinology and Oncology \u201cG. Salvatore\u201d, National Research Council (CNR), via Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3291-0589","authenticated-orcid":false,"given":"Carmen","family":"Moccia","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5545-3048","authenticated-orcid":false,"given":"Elena","family":"Amendola","sequence":"additional","affiliation":[{"name":"Institute of Experimental Endocrinology and Oncology \u201cG. Salvatore\u201d, National Research Council (CNR), via Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"D\u2019Avino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Di Guida","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Clery","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelaide","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"},{"name":"CEINGE Advanced Biotechnology S.C.AR.L., via Gaetano Salvatore 486, 80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-6457","authenticated-orcid":false,"given":"Claudio","family":"Bellevicine","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-8725","authenticated-orcid":false,"given":"Mario","family":"De Felice","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"},{"name":"Institute of Experimental Endocrinology and Oncology \u201cG. Salvatore\u201d, National Research Council (CNR), via Pansini, 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-1174","authenticated-orcid":false,"given":"Gabriella","family":"De Vita","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, via Pansini 5, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.amjsurg.2012.07.027","article-title":"A novel combination of withaferin A and sorafenib shows synergistic efficacy against both papillary and anaplastic thyroid cancers","volume":"204","author":"Cohen","year":"2012","journal-title":"Am. J. 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