A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma

Cells

Christina Bothou¹  Stefan R. Bornstein¹  Constanze Hantel¹  David Penton²  Deborah Cosentini³  Alfredo Berruti³  Mirko Peitzsch⁴  Sandra Sigala⁵  Andrea Abate⁵  Guido A. M. Tiberio⁶ 

[1] Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zürich, Switzerland;Electrophysiology Facility (e-phac), Department of Molecular Life Sciences, University of Zurich (UZH), 8057 Zürich, Switzerland;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;Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany;Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, 25124 Brescia, Italy;Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, 25124 Brescia, Italy;

关键词: adrenocortical carcinoma cell lines;    steroidogenesis;    electrophysiology;    genotype;    NCI-H295;    MUC-1;   

DOI  :  10.3390/cells11091439

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown