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

Sandra Sigala; Christina Bothou; David Penton; Andrea Abate; Mirko Peitzsch; Deborah Cosentini; Guido A M Tiberio; Stefan R Bornstein; Alfredo Berruti; Constanze Hantel

doi:10.3390/cells11091439

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

Cells. 2022 Apr 24;11(9):1439. doi: 10.3390/cells11091439.

Authors

Sandra Sigala¹, Christina Bothou², David Penton³, Andrea Abate¹, Mirko Peitzsch⁴, Deborah Cosentini⁵, Guido A M Tiberio⁶, Stefan R Bornstein^{2

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10}, Alfredo Berruti⁵, Constanze Hantel^{2

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Affiliations

¹ Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, 25124 Brescia, Italy.
² Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), 8091 Zürich, Switzerland.
³ Electrophysiology Facility (e-phac), Department of Molecular Life Sciences, University of Zurich (UZH), 8057 Zürich, Switzerland.
⁴ Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany.
⁵ 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.
⁶ Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, 25124 Brescia, Italy.
⁷ Diabetes and Nutritional Sciences, King's College London, London WC2R 2LS, UK.
⁸ Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
⁹ Paul-Langerhans-Institute Dresden, Helmholtz Center Munich, University Hospital Carl Gustav Carus, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
¹⁰ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore.

Abstract

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.

Keywords: MUC-1; NCI-H295; TVBF-7; adrenocortical carcinoma cell lines; electrophysiology; genotype; steroidogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Hormones
Adrenal Cortex Neoplasms* / metabolism
Adrenal Cortex* / metabolism
Adrenal Cortex* / pathology
Adrenocortical Carcinoma* / genetics
Aldosterone / metabolism
Dehydroepiandrosterone
Humans
Steroid 21-Hydroxylase / metabolism

Substances

Adrenal Cortex Hormones
Dehydroepiandrosterone
Aldosterone
CYP21A2 protein, human
Steroid 21-Hydroxylase