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

Autor(es):Mostrar menos -

Cavalcante, Isadora P. ^[1] ; Nishi, Mirian ^[2] ; Zerbini, Maria Claudia N. ^[3] ; Almeida, Madson Q. ^{[2, 4]} ; Brondani, Vania B. ^{[2, 4]} ; Anhaia de Arruda Botelho, Maria Luiza ^[3] ; Tanno, Fabio Y. ^[5] ; Srougi, Victor ^[5] ; Chambo, Jose Luis ^[5] ; Mendonca, Berenice B. ^{[2, 4]} ; Bertherat, Jerome ^[6] ; Lotfi, Claudimara F. P. ^[1] ; Fragoso, Maria Candida B. V. ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Lab Hormone & Mol Genet LIM 42, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Pathol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Discipline Endocrinol & Metab, Adrenal Unit, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Dept Urol, Sao Paulo, SP - Brazil

^[6] Univ Paris 05, Serv Endocrinol, Hop Cochin, Inst Cochin, CNRS 8104, Ctr Reference Malad Rares Surrenale, INSERM U 1016, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 460, n. C, p. 36-46, JAN 15 2018.
• Citações Web of Science: 9

Resumo

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. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/50192-9 - Avanços na compreensão da fisiopatologia da hiperplasia macronodular adrenocortical primária - PMAH (GP-PMAH)
• Beneficiário: Maria Candida Barisson Villares Fragoso
• Linha de fomento: Auxílio à Pesquisa - Temático