The role of CREB as a proto-oncogene in hematopoiesis.
Cell Cycle
; 4(9): 1134-5, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16096372
ABSTRACT
Cyclic-AMP response element binding protein (CREB) is a transcription factor that functions in glucose homeostasis, growth-factor- dependent cell survival, proliferation and memory. Signaling by hematopoietic growth factors, such as GM-CSF, results in activation of CREB and upregulation of CREB target genes. Data from our laboratory shows that a majority of patients with acute lymphoid and myeloid leukemia overexpress CREB in the bone marrow. CREB overexpression is associated with poor initial outcome of clinical disease in AML patients. To study its role in hematopoiesis, we overexpressed CREB in leukemia cell lines and in mice. CREB overexpression resulted in increased survival and proliferation of myeloid cells and blast-transformation of bone marrow progenitor cells from transgenic mice expressing CREB in the myeloid lineage. CREB transgenic mice also develop myeloproliferative disease after one year. Thus, CREB acts as a proto-oncogene to regulate hematopoiesis and contributes to the leukemia phenotype. Our results suggest that CREB-dependent pathways may serve as targets for directed therapies in leukemia in the future.
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Base de dados:
MEDLINE
Assunto principal:
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Hematopoese
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos