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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 γ-secretase Inhibitors
Author: Silva A.
Jotta P.Y.
Silveira A.B.
Ribeiro D.
Brandalise S.R.
Yunes J.A.
Barata J.T.
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 DAPT 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. © 2010 Ferrata Storti Foundation.
Rights: aberto
Identifier DOI: 10.3324/haematol.2009.011999
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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