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Type: Artigo de periódico
Title: Regulation of PTEN by CK2 and Notch1 in primary T-cell acute lymphoblastic leukemia: rationale for combined use of CK2-and gamma-secretase inhibitors
Author: Silva, A
Jotta, PY
Silveira, AB
Ribeiro, D
Brandalise, SR
Yunes, JA
Barata, JT
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN. However, it is not clear whether NOTCH1 mutations associate with decreased PTEN expression in primary T-ALL. Here, we compared patients with or without NOTCH1 mutations and report that the former presented higher MYC transcript levels and decreased PTEN mRNA expression. We recently showed that T-ALL cells frequently display CK2-mediated PTEN phosphorylation, resulting in PTEN protein stabilization and concomitant functional inactivation. Accordingly, the T-ALL samples analyzed, irrespectively of their NOTCH1 mutational status, expressed significantly higher PTEN protein levels than normal controls. To evaluate the integrated functional impact of Notch transcriptional and CK2 post-translational inactivation of PTEN, we treated T-ALL cells with both the gamma-secretase inhibitor DAFT and the CK2 inhibitors DRB/TBB. Our data suggest that combined use of gamma-secretase and CK2 inhibitors may have therapeutic potential in T-ALL.
Subject: NOTCH1
protein stabilization
CK2 inhibitors
Country: Itália
Editor: Ferrata Storti Foundation
Citation: Haematologica-the Hematology Journal. Ferrata Storti Foundation, v. 95, n. 4, n. 674, n. 678, 2010.
Rights: fechado
Identifier DOI: 10.3324/haematol.2009.011999
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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