MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Pereira, SS (Autor) Outra; Monteiro, M (Autor) ICBAS; Costa, MM (Autor) Outra; J Ferreira (Autor) FMUP; Alves, MG (Autor) Outra; Oliveira, PF (Autor) FMUP; Jarak, I (Autor) Outra; Pignatelli, D (Autor) Outra

Revista

Título: Journal of Cellular Biochemistry

Vol. 120

Páginas: 894-906

ISSN: 0730-2312

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 16 Citações

Scopus - 16 Citações

Outras Informações

ID Authenticus: P-00P-M4S

DOI: 10.1002/jcb.27451

Abstract (EN): Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen-activated protein kinase (MAPK) signaling pathways (extracellular signal-regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 mu M), a specific MEK-MAPK-ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 +/- 0.17) compared with NAG (1.00 +/- 0.19 "arbitrary units"), INC (1.20 +/- 0.13) and BCS (2.09 +/- 0.09). Phospho-p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK-MAPK-ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.

Idioma: Inglês

Tipo (Avaliação Docente): Divulgação

Nº de páginas: 13