{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:03:59Z","timestamp":1758704639807},"reference-count":36,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:p>Context: Anaplastic thyroid carcinomas (ATC) are among the most aggressive human malignancies and are characterized by high mitotic activity. Minichromosome maintenance proteins (MCM) 2\u20137 are required to initiate eukaryotic DNA replication, and their overexpression has been associated with dysplasia and malignancy.<\/jats:p><jats:p>Objective: In an attempt to cast light on the mechanisms governing ATC, we evaluated MCM5 and MCM7 expression in human normal, papillary (PTC), and anaplastic thyroid samples, as well as in primary culture cells and transgenic mouse models.<\/jats:p><jats:p>Results: MCM5 and MCM7 expression was high in 65% of ATC and negligible in normal thyroid tissue and papillary thyroid carcinomas. In ATC, high MCM5 and MCM7 expression was paralleled by high levels of MCM2 and MCM6. An analysis of human ATC primary cell cultures and of a transgenic mouse model of ATC confirmed these findings. An increased transcription rate accounted for MCM7 up-regulation, because the activity of the MCM7 promoter was more than 10-fold higher in ATC cells compared with normal thyroid cells. Adoptive overexpression of wild-type p53, but not of its inactive (R248W and R273H) mutants, strongly down-regulated transcription from the MCM7 promoter, suggesting that p53 knock-out contributes to MCM7 up-regulation in ATC. Treatment with small inhibitory duplex RNAs, which decrease MCM7 protein levels, reduced the rate of DNA synthesis in ATC cells.<\/jats:p><jats:p>Conclusion: MCM proteins are overexpressed in ATC and sustain the high proliferative capacity of ATC cells.<\/jats:p>","DOI":"10.1210\/jc.2004-2459","type":"journal-article","created":{"date-parts":[[2005,8,8]],"date-time":"2005-08-08T21:37:43Z","timestamp":1123537063000},"page":"4703-4709","source":"Crossref","is-referenced-by-count":34,"title":["Mitogenic Effects of the Up-Regulation of Minichromosome Maintenance Proteins in Anaplastic Thyroid Carcinoma"],"prefix":"10.1210","volume":"90","author":[{"given":"Teresa","family":"Guida","sequence":"first","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]},{"given":"Giuliana","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]},{"given":"Pinuccia","family":"Faviana","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia (P.F., R.G., F.B.), Universita\u0300 di Pisa, 56126 Pisa, Italy"}]},{"given":"Riccardo","family":"Giannini","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia (P.F., R.G., F.B.), Universita\u0300 di Pisa, 56126 Pisa, Italy"}]},{"given":"Ginesa","family":"Garcia-Rostan","sequence":"additional","affiliation":[{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (G.G.-R.), 4200-465 Porto, Portugal"}]},{"given":"Livia","family":"Provitera","sequence":"additional","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]},{"given":"Fulvio","family":"Basolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncologia (P.F., R.G., F.B.), Universita\u0300 di Pisa, 56126 Pisa, Italy"}]},{"given":"Alfredo","family":"Fusco","sequence":"additional","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]},{"given":"Francesca","family":"Carlomagno","sequence":"additional","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]},{"given":"Massimo","family":"Santoro","sequence":"additional","affiliation":[{"name":"Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano (T.G., G.S., L.P., A.F., F.C., M.S.), Universita\u0300 Federico II, 80131 Naples, Italy"}]}],"member":"80","reference":[{"key":"2020071615530259300_R1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0140-6736(03)12488-9","article-title":"Thyroid carcinoma.","volume":"361","author":"Sherman","year":"2003","journal-title":"Lancet"},{"key":"2020071615530259300_R2","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1067\/msy.2001.118266","article-title":"Anaplastic thyroid carcinoma: a 50-year experience at a single institution.","volume":"130","author":"McIver","year":"2001","journal-title":"Surgery"},{"key":"2020071615530259300_R3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/(SICI)1098-2388(199901\/02)16:1<64::AID-SSU10>3.0.CO;2-U","article-title":"Anaplastic thyroid carcinoma: a therapeutic challenge.","volume":"16","author":"Ain","year":"1999","journal-title":"Semin Surg Oncol"},{"key":"2020071615530259300_R4","first-page":"77","article-title":"Undifferentiated (anaplastic) carcinoma","author":"Ordonez","year":"2004","journal-title":"In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, eds. 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