Differential Expression of Bcl-2 Family Proteins Determines the Sensitivity of Human Follicular Lymphoma Cells to Dexamethasone-mediated and Anti-BCR-mediated Apoptosis.
J Immunother
; 39(1): 8-14, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26641257
ABSTRACT
Bcl-2 family comprises proapoptotic and antiapoptotic proteins. The balance between these proteins is critical for the survival of the cells. Overexpression of the antiapoptotic protein, Bcl-2, is the hallmark of follicular lymphoma (FL). High expression of Bcl-2 provides survival advantage and may facilitate chemotherapeutic resistance in FL. In the present study, we examined expression profile of Bcl-2 family proteins such as Bcl-2, Bcl-xL, and Bim in human FL cell lines, HF1A3 and HF28. We assessed the correlation between the expression levels of these proteins and cells' sensitivity to dexamethasone (Dex)-mediated and B-cell receptor (BCR)-mediated apoptosis. Here, we show that Dex and anti-BCR-induced synergistic apoptosis which correlated with significant downregulation of Bcl-xL, inhibition of ERK1/2 phosphorylation and accumulation of nonphosphorylated Bim. However, HF28 cells were less sensitive than HF1A3 cells to Dex-induced and anti-BCR-induced apoptosis due to high Bcl-2 protein level. It is interesting to note that, a Bcl-2-specific inhibitor, ABT-199, sensitized HF28 cells to Dex-induced or anti-BCR-induced apoptosis. In addition, overexpression of Bcl-xL prevented Dex-mediated, anti-BCR-mediated, and ABT-199-mediated apoptosis, indicating that mitochondria were involved. In conclusion, these data show that the expression levels of Bcl-2 family proteins may serve to predict tumor response to BH3 mimetics and the sensitivity of FL cells to Dex-induced and anti-BCR-induced apoptosis. Moreover, our results show that BCR-targeted apoptosis might have therapeutic benefit against FL and B-cell lymphomas.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dexametasona
/
Receptores de Antígenos de Linfócitos B
/
Regulação Neoplásica da Expressão Gênica
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Linfoma Folicular
/
Apoptose
/
Antineoplásicos Hormonais
/
Proteínas Proto-Oncogênicas c-bcl-2
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunother
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Finlândia