Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect.
Int J Oncol
; 51(2): 456-466, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28586009
ABSTRACT
The ETS transcription factors play a critical role during hematopoiesis. In F-MuLV-induced erythroleukemia, Fli1 insertional activation producing high expression of this transcription factor required to promote proliferation. How deregulated Fli1 expression alters the balance between erythroid differentiation and proliferation is unknown. To address this issue, we exogenously overexpressed Fli1 in an erythroleukemic cell harboring activation of spi1/PU.1, another ETS gene involved in erythroleukemogenesis. While the proliferation in culture remains unaffected, Fli1 overexpression imparts morphological and immunohistochemical characteristics of immature erythroid progenitors. Fli1 overexpression in erythroleukemic cells increased the numbers of erythroid colonies on methylcellulose and reduced tumorigenicity as evidenced by increase latency of erythroleukemogenesis in mice inoculated with these cells. Although all transplanted mice developed enlargement of the spleen and liver due to leukemic infiltration, Fli1 overexpression altered the hematopoietic phenotype, significantly increasing the expression of regulatory hematopoietic genes cKIT, SCA-1, CD41 and CD71. In contrast, expression of Spi1/PU.1 in a Fli1 producing erythroleukemia cell line in which fli1 is activated, resulted in increased proliferation through activation of growth promoting proteins MAPK, AKT, cMYC and JAK2. Importantly, these progenitors express high levels of markers such as CD71 and TER119 associated with more mature erythroid cells. Thus, Fli1 overexpression induces a de-differentiation program by reverting CFU-E to BFU-E erythroid progenitor activity, while Spi1/PU.1 promoting maturation from BFU-E to CFU-E.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Eritroblástica Aguda
/
Proteínas de Ligação a DNA
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Proteína Proto-Oncogênica c-fli-1
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Proteínas de Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Canadá