{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:01:37Z","timestamp":1788930097685,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T00:00:00Z","timestamp":1650758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017659","name":"Uniscientia Foundation","doi-asserted-by":"publisher","award":["Tumor Model"],"award-info":[{"award-number":["Tumor Model"]}],"id":[{"id":"10.13039\/501100017659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heuberg Foundation","award":["Novel multidimensional models for the adrenal gland and adrenal tumors"],"award-info":[{"award-number":["Novel multidimensional models for the adrenal gland and adrenal tumors"]}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["to Alfredo Berruti"],"award-info":[{"award-number":["to Alfredo Berruti"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Adrenocortical carcinoma is a heterogeneous and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. In this study, we have assessed for the preclinical gold standard NCI-H295 in direct comparison with the more recently established MUC-1 and a here newly reported ACC cell line (TVBF-7) the mutational status of important driver genes (TP53, MEN1, PRKAR1A, CTNNB1, APC, ZNRF-3, IGF-2, EGFR, RB1, BRCA1, BRCA2, RET, GNAS and PTEN), Wnt-signaling specificities (CTNNB1 mutation vs. APC mutation vs. wildtype), steroidogenic-(CYP11A1, CYP17A1, HSD3B2, HSD17B4, CYP21A2, CYP11B1, CYP11B2, MC2R, AT1R) and nuclear-receptor-signaling (AR, ER, GCR), varying electrophysiological potentials as well as highly individual hormone secretion profiles (Cortisol, Aldosterone, DHEA, DHEAS, Testosterone, 17-OH Progesterone, among others) which were investigated under basal and stimulated conditions (ACTH, AngII, FSK). Our findings reveal important genetic and pathophysiological characteristics for these three cell lines and reveal the importance of such cell-line panels reflecting differential endocrine functionalities to thereby better reflect clinically well-known ACC patient heterogeneities in preclinical studies.<\/jats:p>","DOI":"10.3390\/cells11091439","type":"journal-article","created":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T22:22:41Z","timestamp":1650838961000},"page":"1439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-4121","authenticated-orcid":false,"given":"Sandra","family":"Sigala","sequence":"first","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-7140","authenticated-orcid":false,"given":"Christina","family":"Bothou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Penton","sequence":"additional","affiliation":[{"name":"Electrophysiology Facility (e-phac), Department of Molecular Life Sciences, University of Zurich (UZH), 8057 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-0916","authenticated-orcid":false,"given":"Andrea","family":"Abate","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-675X","authenticated-orcid":false,"given":"Mirko","family":"Peitzsch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Cosentini","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili di Brescia, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-1179","authenticated-orcid":false,"given":"Guido","family":"Tiberio","sequence":"additional","affiliation":[{"name":"Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Z\u00fcrich, Switzerland"},{"name":"Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany"},{"name":"Diabetes and Nutritional Sciences, King\u2019s College London, London WC2R 2LS, UK"},{"name":"Center for Regenerative Therapies, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Paul-Langerhans-Institute Dresden, Helmholtz Center Munich, University Hospital Carl Gustav Carus, Faculty of Medicine, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-0043","authenticated-orcid":false,"given":"Alfredo","family":"Berruti","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili di Brescia, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Z\u00fcrich, Switzerland"},{"name":"Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, 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