Bptf determines oncogenic addiction in aggressive B-cell lymphomas.
Oncogene
; 39(25): 4884-4895, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32451433
ABSTRACT
Chromatin remodeling factors contribute to establish aberrant gene expression programs in cancer cells and therefore represent valuable targets for therapeutic intervention. BPTF (Bromodomain PhD Transcription Factor), a core subunit of the nucleosome remodeling factor (NURF), modulates c-MYC oncogenic activity in pancreatic cancer. Here, we analyze the role of BPTF in c-MYC-driven B-cell lymphomagenesis using the Eµ-Myc transgenic mouse model of aggressive B-cell lymphoma. We find that BPTF is required for normal B-cell differentiation without evidence of haploinsufficiency. In contrast, deletion of one Bptf allele is sufficient to delay lymphomagenesis in Eµ-Myc mice. Tumors arising in a Bptf heterozygous background display decreased c-MYC levels and pathway activity, together with increased activation of the NF-κB pathway, a molecular signature characteristic of human diffuse large B-cell lymphoma (DLBCL). In human B-cell lymphoma samples, we find a strong correlation between BPTF and c-MYC mRNA and protein levels, together with an anti-correlation between BPTF and NF-κB pathway activity. Our results indicate that BPTF is a relevant therapeutic target in B-cell lymphomas and that, upon its inhibition, cells acquire distinct oncogenic dependencies.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Linfoma de Células B
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Proteínas Proto-Oncogênicas c-myc
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Antígenos Nucleares
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Vício Oncogênico
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article