2. Academic Validation
  3. The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

  • Mol Cell Endocrinol. 2018 Jan 15;460:36-46. doi: 10.1016/j.mce.2017.06.027.
Isadora P Cavalcante 1,  Mirian Nishi 2,  Maria Claudia N Zerbini 3,  Madson Q Almeida 4,  Vania B Brondani 4,  Maria Luiza Anhaia de Arruda Botelho 3,  Fabio Y Tanno 5,  Victor Srougi 5,  José Luis Chambo 5,  Berenice B Mendonca 4,  Jérôme Bertherat 6,  Claudimara F P Lotfi 7,  Maria Candida B V Fragoso 4
Affiliations

Affiliations

  • 1 Institute of Biomedical Sciences, Department of Anatomy, University of Sao Paulo, SP, Brazil.
  • 2 Laboratory of Hormone and Molecular Genetic LIM/42, University of Sao Paulo, SP, Brazil.
  • 3 Department of Pathology, University of Sao Paulo, SP, Brazil.
  • 4 Laboratory of Hormone and Molecular Genetic LIM/42, University of Sao Paulo, SP, Brazil; Adrenal Unit, Discipline of Endocrinology & Metabolism, University of Sao Paulo, SP, Brazil.
  • 5 Department of Urology, University of Sao Paulo, SP, Brazil.
  • 6 Service d'Endocrinologie, Hôpital Cochin, Centre de Référence Maladies Rares de la Surrénale, Institut Cochin, INSERM U 1016, CNRS 8104, Université Paris Descartes, Paris, France.
  • 7 Institute of Biomedical Sciences, Department of Anatomy, University of Sao Paulo, SP, Brazil. Electronic address: clotfi@usp.br.
PMID: 28676429 DOI: 10.1016/j.mce.2017.06.027
Abstract

The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.

Keywords

ARMC5; Adrenocortical hyperplasia; Cell cultures (5 words); Cushing syndrome; PMAH.

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