An ets2-driven transcriptional program in tumor-associated macrophages promotes tumor metastasis.
Cancer Res
; 70(4): 1323-33, 2010 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-20145133
ABSTRACT
Tumor-associated macrophages (TAM) are implicated in breast cancer metastasis, but relatively little is known about the underlying genes and pathways that are involved. The transcription factor Ets2 is a direct target of signaling pathways involved in regulating macrophage functions during inflammation. We conditionally deleted Ets in TAMs to determine its function at this level on mouse mammary tumor growth and metastasis. Ets2 deletion in TAMs decreased the frequency and size of lung metastases in three different mouse models of breast cancer metastasis. Expression profiling and chromatin immunoprecipitation assays in isolated TAMs established that Ets2 repressed a gene program that included several well-characterized inhibitors of angiogenesis. Consistent with these results, Ets2 ablation in TAMs led to decreased angiogenesis and decreased growth of tumors. An Ets2-TAM expression signature consisting of 133 genes was identified within human breast cancer expression data which could retrospectively predict overall survival of patients with breast cancer in two independent data sets. In summary, we identified Ets2 as a central driver of a transcriptional program in TAMs that acts to promote lung metastasis of breast tumors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Neoplasias Mamárias Animais
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Proteína Proto-Oncogênica c-ets-2
/
Macrófagos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos