Overexpression of Lhx2 suppresses proliferation of human T cell acute lymphoblastic leukemia-derived cells, partly by reducing LMO2 protein levels.
Biochem Biophys Res Commun
; 495(3): 2310-2316, 2018 01 15.
Article
em En
| MEDLINE
| ID: mdl-29278703
ABSTRACT
T cell acute lymphoblastic leukemia (T-ALL) is a malignant cancer with poor prognosis. The transcriptional co-factor LIM domain only 2 (LMO2) and its target gene HHEX are essential for self-renewal of T cell precursors and T-ALL etiology. LMO2 directly associates with LDB1 in a large DNA-containing nuclear complex and controls the transcription of T-ALL-related genes. Recently, we reported that overexpression of the LIM-homeodomain transcription factor, Lhx2, results in liberation of the Lmo2 protein from the Lmo2-Ldb1 complex, followed by ubiquitin proteasome mediated degradation. Here, we found that proliferation of five human T-ALL-derived cell lines, including CCRF-CEM, was significantly suppressed by retroviral overexpression of Lhx2. The majority of Lhx2-transduced CCRF-CEM cells arrested in G0 phase and subsequently underwent apoptosis. Expression of LMO2 protein as well as HHEX, ERG, HES1 and MYC genes was repressed in CCRF-CEM cells by transduction with Lhx2. Lhx2-mediated growth inhibition was partially rescued by simultaneous overexpression of Lmo2; however, both the C-terminal LIM domain and the homeodomain of Lhx2 were required for its growth-suppressive activity. These data indicate that Lhx2 is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means. We propose Lhx2 as a new molecular tool for anti-T-ALL drug development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Proto-Oncogênicas
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Proteínas com Homeodomínio LIM
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Proteínas com Domínio LIM
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão