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

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Citações na Scopus
37
Tipo de produção
article
Data de publicação
2018
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER IRELAND LTD
Citação
MOLECULAR AND CELLULAR ENDOCRINOLOGY, v.460, n.C, p.36-46, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
Palavras-chave
Cushing syndrome, PMAH, Adrenocortical hyperplasia, ARMC5, Cell cultures (5 words)
Referências
  1. Alencar G.A., 2014, J CLIN ENDOCR METAB
  2. Antonini Sonir R., 2004, Arq Bras Endocrinol Metab, V48, P620, DOI 10.1590/S0004-27302004000500006
  3. Assie G, 2013, NEW ENGL J MED, V369, P2105, DOI 10.1056/NEJMoa1304603
  4. Bialik S, 2006, ANNU REV BIOCHEM, V75, P189, DOI 10.1146/annurev.biochem.75.103004.142615
  5. Bourdeau I, 2004, ENDOCR RES, V30, P575, DOI 10.1081/ERC-200043735
  6. Bourdeau I, 2002, ANN NY ACAD SCI, V968, P240, DOI 10.1111/j.1749-6632.2002.tb04339.x
  7. Bourdeau I, 2016, EUR J ENDOCRINOL, V174, P85, DOI 10.1530/EJE-15-0642
  8. Boutillier A L, 1998, Pituitary, V1, P33, DOI 10.1023/A:1009966808106
  9. Correa R, 2015, EUR J ENDOCRINOL, V173, P435, DOI 10.1530/EJE-15-0205
  10. de Joussineau C, 2012, MOL CELL ENDOCRINOL, V351, P28, DOI 10.1016/j.mce.2011.10.006
  11. Drougat L, 2015, FRONT ENDOCRINOL, V6, DOI 10.3389/fendo.2015.00096
  12. Faucz F.R., 2014, J CLIN ENDOCR METAB
  13. Fujii H, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0110543
  14. Gagliardi L, 2014, J CLIN ENDOCR METAB, V99, pE1784, DOI 10.1210/jc.2014-1265
  15. Hu Y, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms13834
  16. Iwata M, 2012, INTERNAL MED, V51, P2181, DOI 10.2169/internalmedicine.51.7547
  17. KELLERWOOD ME, 1984, ENDOCR REV, V5, P1, DOI 10.1210/edrv-5-1-1
  18. KIRSCHNER MA, 1964, J CLIN ENDOCR METAB, V24, P947, DOI 10.1210/jcem-24-10-947
  19. Kovalovsky D, 2002, MOL ENDOCRINOL, V16, P1638, DOI 10.1210/me.16.7.1638
  20. Lacroix A, 2001, ENDOCR REV, V22, P75, DOI 10.1210/er.22.1.75
  21. Lacroix A, 1997, NEW ENGL J MED, V337, P1429, DOI 10.1056/NEJM199711133372004
  22. Lacroix A, 2010, CLIN ENDOCRINOL, V73, P1, DOI 10.1111/j.1365-2265.2009.03689.x
  23. Lacroix A, 2009, BEST PRACT RES CL EN, V23, P245, DOI 10.1016/j.beem.2008.10.011
  24. LEBRETHON MC, 1994, MOL CELL ENDOCRINOL, V106, P137, DOI 10.1016/0303-7207(94)90195-3
  25. Lefebvre H, 2003, J CLIN ENDOCR METAB, V88, P3035, DOI 10.1210/jc.2002-030014
  26. Lefebvre H, 2016, FRONT ENDOCRINOL, V7, DOI 10.3389/fendo.2016.00098
  27. Lefebvre H, 2015, FRONT ENDOCRINOL, V6, DOI 10.3389/fendo.2015.00034
  28. Lodish M, 2016, NAT REV ENDOCRINOL, V12, P255, DOI 10.1038/nrendo.2016.24
  29. Louiset E, 2006, J CLIN ENDOCR METAB, V91, P4578, DOI 10.1210/jc.2006-0538
  30. Louiset E, 2013, NEW ENGL J MED, V369, P2115, DOI 10.1056/NEJMoa1215245
  31. Mattos GE, 2011, CELL TISSUE RES, V345, P343, DOI 10.1007/s00441-011-1220-8
  32. Mazzuco TL, 2007, ARQ BRAS ENDOCRINOL, V51, P1452, DOI 10.1590/S0004-27302007000900007
  33. Morioka M, 1997, ENDOCR J, V44, P65, DOI 10.1507/endocrj.44.65
  34. REDDY GPV, 1994, J CELL BIOCHEM, V54, P379, DOI 10.1002/jcb.240540404
  35. SASANO H, 1994, MODERN PATHOL, V7, P215
  36. Srougi V, 2016, UROLOGY, V90, P217, DOI 10.1016/j.urology.2015.11.043
  37. Tewari R, 2010, TRENDS CELL BIOL, V20, P470, DOI 10.1016/j.tcb.2010.05.003
  38. Xing YW, 2010, J MOL ENDOCRINOL, V45, P59, DOI 10.1677/JME-10-0006