Bcl-X is the major pleiotropic anti-apoptotic gene activated by retroviral insertion mutagenesis in an IL-3 dependent bone marrow derived cell line

Thomas, Jean‐Claude; Leverrier, Yann; Marvel, Jacqueline

doi:10.1038/sj.onc.1201672

Cited by 24 publications

(22 citation statements)

References 33 publications

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“…STAT5 activation has been also observed in a T cell line upon treatment with an anti-apoptotic reagent or in Ba/F3 cells transformed by the bcr-abl oncogene that promotes a strong anti-apoptotic e ect (Rui et al, 1998;Ahmed et al, 1998) indicating that STAT5 in these di erent situations might be an inhibitor of apoptosis. The reduction of Bcl-x expression but not that of Bcl-2 precedes the onset of apoptosis in T cells after IL-2 withdrawal and in Ba/F3 cells after IL-3 withdrawal and is thought to be a major pleiotropic anti-apoptotic gene in Ba/F3 cells (Broome et al, 1995;Leverrier et al, 1997;Thomas et al, 1998). This is in agreement with our results showing the dramatic reduction of Bcl-x expression in Ba/F3D749 cells in absence of IL-3.…”

Section: Discussionmentioning

confidence: 99%

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

et al. 1999

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Section: Discussionmentioning

confidence: 99%

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

et al. 1999

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“…Therefore, we have tested the effect of antiapoptotic genes bcl-X and nr-13 expression on Sp1-induced apoptosis in Baf-3 cells. Two days after infection, Sp1-transduced Baf-3 cells overexpressing bcl-X or nr-13 genes (Mangeney et al, 1996;Thomas et al, 1998) displayed reduced phosphatidylserine externalization compared to Sp1-transduced parental Baf-3 cells (Figure 2d). Therefore, Sp1 activates an apoptotic pathway in Baf-3 cells that is sensitive to inhibition by Bcl-2 family members.…”

Section: Sp1 Overexpression Induces Apoptosismentioning

confidence: 95%

“…Baf-3 cells overexpressing the antiapoptotic genes bcl-x (Baf-Bcl-X) and nr-13 (Baf-Nr-13) have been characterized previously (Mangeney et al, 1996;Thomas et al, 1998). 3T3 fibroblasts and the retrovirus packaging Phoenix cell line (GC Promochem Sarl, Molsheim, France) were maintained in DMEM containing 10% FCS and 2 mM L-glutamine.…”

Section: Cell Culturementioning

confidence: 99%

Overexpression of Sp1 transcription factor induces apoptosis

et al. 2006

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Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.

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“…22,23 To determine if Figure 4 Glycolysis inhibition does not affect the activation of the PI3-kinase/Akt pathway or Bcl-X expression. Baf-3 cells were cultured for 8 h in DMEM or in a low glucose medium containing or not 6 mM 2-deoxy-D-Glucose, in the presence or in the absence of IL-3.…”

Section: Constitutive Bcl-x Expression Protects Baf-3 Cells From Apopmentioning

confidence: 99%

Decreased glycolytic metabolism contributes to but is not the inducer of apoptosis following IL-3-starvation

et al. 2002

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IL-3 regulates the glycolytic pathway. In Baf-3 cells IL-3 starvation leads to a decrease in glucose uptake and in lactate production. To determine if there is a link between the decreased metabolism induced by growth factor-starvation and the induction of cell death, we have compared the cell death characteristics and the metabolic modifications induced by IL-3-deprivation or glucose-deprivation in Baf-3 cells. We show that in both conditions cells die by an apoptotic process which involves the activation of similar Caspases. Different metabolic parameters (i.e. intracellular ATP levels and lactate accumulation in the culture medium) were measured. We show that IL-3 deprivation leads to a partial decrease in lactate production in contrast to glucose deprivation that completely inhibits lactate production. Similarly following IL-3-starvation a significant drop in the intracellular ATP levels in live cells is observed only after 16 h when a large fraction, more than 50 per cent of cells, is already apoptotic. On the contrary, glucose deprivation is followed by an abrupt decrease in ATP levels in the first 2 h of treatment. However, in the presence of IL-3, cells are able to survive for an extended time in these conditions since 70% of cells survived with low ATP levels for up to 16 h. This was not due to partial inhibition of the apoptotic process by the low level of ATP as glucose-deprivation in the absence of IL-3 led to faster death kinetics of Baf-3 cells compared with IL-3 starvation only. These results indicate that the drop in ATP levels and the triggering of apoptosis can be dissociated in time and that when the glycolytic pathway is strongly inhibited, cells are able to survive with relatively low ATP levels if IL-3 is present. Finally we show that induction of bcl-x by IL-3 protects cells from glucose-deprivation induced cell death.

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Bcl-X is the major pleiotropic anti-apoptotic gene activated by retroviral insertion mutagenesis in an IL-3 dependent bone marrow derived cell line

Cited by 24 publications

References 33 publications

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Overexpression of Sp1 transcription factor induces apoptosis

Decreased glycolytic metabolism contributes to but is not the inducer of apoptosis following IL-3-starvation

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