Glucocorticoid receptor knock down reveals a similar apoptotic threshold but differing gene regulation patterns in T-cell and pre-B-cell acute lymphoblastic leukemia.
Mol Cell Endocrinol
; 320(1-2): 76-86, 2010 May 14.
Article
em En
| MEDLINE
| ID: mdl-20170710
ABSTRACT
Glucocorticoids (GCs) are used in combination therapy for treating acute lymphoblastic leukemia (ALL). In T-cell (CEM-C7) and pre-B-cell (697) ALL cell lines, dexamethasone (Dex) treatment causes an auto-upregulation of glucocorticoid receptor (GR) mRNA transcripts and protein. We hypothesized that there is a threshold level of GR transcripts/protein needed for cells to respond to the apoptosis-inducing effects of hormone. GR knock down using a doxycycline-controllable shRNAmir indicated that the apoptotic response changes from sensitive to resistant with changing GR levels. Titration of the 697 cell GR to equal that of the CEM-C7 T-cell ALL line caused a shift in sensitivity to that seen in CEM-C7 cells. While the same level of GR is required to trigger apoptosis in both T-cell and pre-B-cell ALL lineages, similarities and differences were observed for the regulation of target genes in these lineages. These preliminary gene regulation patterns may lead to the development of a molecular signature for GC-sensitive and GC-resistant leukemia cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Receptores de Glucocorticoides
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Regulação Leucêmica da Expressão Gênica
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Apoptose
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Técnicas de Silenciamento de Genes
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article