Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation.
Leukemia
; 29(4): 901-8, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25252870
ABSTRACT
HOX homeobox proteins are key oncogenic drivers in hematopoietic malignancies. Here we demonstrate that HOXA1, HOXA6 and predominantly HOXA9 are able to induce the production of insulin-like growth factor 1 (Igf1). In chromatin immunoprecipitations, HOXA9 bound directly to the putative promoter and a DNase-hypersensitive region in the first intron of the Igf1 gene. Transcription rates of the Igf1 gene paralleled HOXA9 activity. Primary cells transformed by HOXA9 expressed functional Igf1 receptors and activated the protein kinase Akt in response to Igf1 stimulation, suggesting the existence of an autocrine signaling loop. Genomic deletion of the Igf1 gene by Cre-mediated recombination increased sensitivity toward apoptosis after serum starvation. In addition, the leukemogenic potential of Igf1-negative, HOXA9-transformed cells was impaired, leading to a significant delay in disease development on transplantation into recipient animals.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Linfócitos
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Leucemia
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Regulação Leucêmica da Expressão Gênica
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Transformação Celular Neoplásica
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Proteínas de Homeodomínio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha