p53-induced apoptosis in the human T-ALL cell line CCRF-CEM

Geley, Stephan; Hartmann, Bernd L.; Hattmannstorfer, Rosa; Löffler, Markus; Ausserlechner, Michael J.; Bernhard, David; Sgonc, Roswitha; Strasser-Wozak, Elisabeth Mc; Ebner, Maria; Auer, Bernhard; Kofler, Reinhard

doi:10.1038/sj.onc.1201399

Cited by 37 publications

(49 citation statements)

References 36 publications

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“…However, it should be noted that a con¯ictual situation remains with respect to the e ect of this oncogenic protein in TNF-mediated cytotoxicity. Bax expression has been reported to be increased during p53-mediated human hematopoietic cell line CEM apoptosis and appears to be the most promising candidate for the primary p53 response gene in this cell death pathway (Geley et al, 1997). However, we could not detect any change in Bax protein level following infection of TNF-resistant cells with AdWtp53.…”

Section: Discussioncontrasting

confidence: 69%

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

et al. 1999

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Tumor suppressor p53 is a nuclear transcription factor that blocks cell cycle progression and induces apoptosis. We have previously shown that the MCF7 resistance to the cytotoxic action of TNF correlates with p53 mutations. In the present study, we used a recombinant adenovirus carrying a wild-type p53 gene (Adwtp53) in order to investigate the e ect of wt p53 transfer on modulation of cell resistance to the cytotoxic action of TNF. Our data indicate that infection of TNF resistant MCF7 cells (1001 and MCF7/Adr) with Adwtp53 resulted in the restoration of wt p53 expression and function as respectively revealed by the yeast assay and the induction of p53 inducible genes MDM2 and p21. Furthermore, the restoration of p53 function signi®cantly sensitized TNF resistant cells to TNF cytotoxic action. This correlated with a signi®cant down-regulation of cmyc in both TNF-resistant cell lines and a decrease of Retinoblastoma protein (Rb) in 1001 clone. In contrast, the e ect of p53 seems to be independent from Bcl-2 and Bax protein level regulation. The present study suggests that the combination of TNF and Adwtp53 may be a potential strategy to sensitize mutant p53 TNF-resistant tumors to the cytotoxic action of this cytokine.

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Section: Discussioncontrasting

confidence: 69%

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

et al. 1999

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“…39 Briefly, cells were centrifuged and resuspended in a buffer 0.1% Triton X-100, 0.1% sodium-citrate and 0.005% propidium-iodide. Sub-G1 events in the fluorescence channel represent apoptotic nuclei.…”

Section: Determination Of Apoptosismentioning

confidence: 99%

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

et al. 2004

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Glucocorticoids (GC) induce apoptosis in malignant lymphoblasts, but the mechanism of this process as well as that of the clinically important GC resistance is unknown. We investigated GC resistance in Jurkat T-ALL cells in which ectopic GC receptor (GR) restores GC sensitivity, suggesting deficient GR expression. Jurkat cells expressed one wild-type and one mutated (R477H) GR allele. GR R477H ligand-bindingdependent nuclear import, as revealed by live-cell microscopy of YFP-tagged GR, was unaffected. Transactivation and transrepression were markedly impaired; however, GR R477H did not act in a dominant-negative manner, that is, did not prevent cell death, when introduced into a GC-sensitive cell line by retroviral gene transfer. Contrary to another GR heterozygous, but GC-sensitive, T-ALL model (CCRF-CEM), Jurkats expressed lower basal GR levels and did not autoinduce their GR, as revealed by 'real-time' RT-PCR and immunoblotting. Absent GR auto-induction could not be restored by transgenic GR and, hence, was not caused by reduced basal GR levels. Thus, inactivation of one GR gene results in haploinsufficiency if associated with lack of GR auto-induction.

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“…CEM cells overexpressing human Bcl-2 were a gift from David Huang (Walter and Eliza Hall Institute, Melbourne, Australia). CEM cells expressing CrmA have been described (30). Parental FDC-P1 cells and cells overexpressing Bid, Bcl-2, and Bid plus Bcl-2 were a kind gift from D. Huang and were cultured as described (7).…”

Section: Methodsmentioning

confidence: 99%

The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species

Ruefli

Ausserlechner²,

Bernhard³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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460

426

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Many chemotherapeutic agents induce mitochondrial-membrane disruption to initiate apoptosis. However, the upstream events leading to drug-induced mitochondrial perturbation have remained poorly defined. We have used a variety of physiological and pharmacological inhibitors of distinct apoptotic pathways to analyze the manner by which suberoylanilide hydroxamic acid (SAHA), a chemotherapeutic agent and histone deacetylase inhibitor, induces cell death. We demonstrate that SAHA initiates cell death by inducing mitochondria-mediated death pathways characterized by cytochrome c release and the production of reactive oxygen species, and does not require the activation of key caspases such as caspase-8 or -3. We provide evidence that mitochondrial disruption is achieved by means of the cleavage of the BH3-only proapoptotic Bcl-2 family member Bid. SAHA-induced Bid cleavage was not blocked by caspase inhibitors or the overexpression of Bcl-2 but did require the transcriptional regulatory activity of SAHA. These data provide evidence of a mechanism of cell death mediated by transcriptional events that result in the cleavage of Bid, disruption of the mitochondrial membrane, and production of reactive oxygen species to induce cell death.

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p53-induced apoptosis in the human T-ALL cell line CCRF-CEM

Cited by 37 publications

References 36 publications

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species

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