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Low PRKAB2 Expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line.
Xavier, Alcides Euzebio Tavares; Veronez, Luciana Chain; Nagano, Luís Fernando Peinado; Correa, Carolina Alves Pereira; Baroni, Mirela; Ramos, Milena Silva; Queiroz, Rosane de Gomes de Paula; Fernandes Molina, Carlos Augusto; Yunes, José Andres; Brandalise, Silvia Regina; Antonini, Sonir Antonio Rauber; Tone, Luiz Gonzaga; Valera, Elvis Terci; Scrideli, Carlos Alberto.
Afiliação
  • Xavier AET; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Veronez LC; Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
  • Nagano LFP; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Correa CAP; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Baroni M; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Ramos MS; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Queiroz RGP; Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
  • Fernandes Molina CA; Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of Sao Paulo, São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
  • Yunes JA; Boldrini Children's Center, Campinas 13083-210, SP, Brazil.
  • Brandalise SR; Boldrini Children's Center, Campinas 13083-210, SP, Brazil.
  • Antonini SAR; Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
  • Tone LG; Departments of Genetics, Ribeirão Preto Medical School, University of São Paulo, 3000 Bandeirantes Avenue, Ribeirão Preto 14049-900, SP, Brazil.
  • Valera ET; Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
  • Scrideli CA; Departments of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Cancers (Basel) ; 16(6)2024 Mar 08.
Article em En | MEDLINE | ID: mdl-38539429
ABSTRACT
Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. The PRKAB2 gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs. We have evaluated how PRKAB2 is associated with clinical and biological characteristics in 63 pediatric patients with ACTs and conducted in vitro studies on the human NCI-H295R ACC cell line. An analysis of our cohort and the public ACC pediatric dataset GSE76019 showed that lower PRKAB2 expression was associated with relapse, death, metastasis, and lower event-free and overall survival rates. Multivariate analysis showed that PRKAB2 expression was an independent prognostic factor when associated with age, tumor weight and volume, and metastasis. In vitro tests on NCI-H295R cells demonstrated that Rottlerin, a drug that can activate AMPK, modulated several pathways in NCI-H295R cells, including AMPK/mTOR, Wnt/ß-catenin, SKP2, HH, MAPK, NFKB, and TNF. Treatment with Rottlerin decreased cell proliferation and migration, clonogenic capacity, and steroid production. Together, these results suggest that PRKAB2 is a potential prognostic marker in pediatric ACTs, and that Rottlerin is promising for investigating drugs that can act against ACTs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça