Resistance of MCF7 human breast carcinoma cells to TNF-induced cell death is associated with loss of p53 function

Cai, Zhenzi; Capoulade, Corinne; Moyret‐Lalle, Caroline; Amor‐Guéret, Mounira; Feunteun, Jean; Larsen, Annette K.; Paillerets, Brigitte Bressac-de; Chouaı̈b, Salem

doi:10.1038/sj.onc.1201445

Cited by 78 publications

(76 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this context, we have previously shown that while MCF7 has a wt p53 gene, both TNF resistant sublines (1001 and MCF7/ADR) derived from the parental MCF7 cells exhibit mutant p53, resulting in loss of p53 transactivation functions. Furthermore, we have shown that impairment of wild-type p53 function may contribute to cell resistance towards the cytotoxic action of TNF and provided evidence that the disruption of wild-type p53 protein resulted in loss of the cytotoxic activity of TNF (Cai et al, 1997b). It should be noted that MCF7 cells are caspase 3 de®cient (Janicke et al, 1998 and our unpublished results).…”

Section: Discussionsupporting

confidence: 53%

“…For this purpose, we used TNF-sensitive breast adenocarcinoma MCF7 cells and TNF-resistant derivatives 1001 clone and MCF7/ADR cells ( Figure 1a). In a previous study, we have demonstrated a correlation between cell resistance to the cytotoxic action of TNF and p53 function (Cai et al, 1997b). Using SSCP (single-strand conformation polymorphism) analysis and DNA sequencing, we have shown that while MCF7 has a wt p53 gene, both TNF resistant sublines (1001 and MCF7/Adr) derived from the parental MCF7 cells exhibit mutant p53.…”

Section: Functional Wt P53 Expression Following Adwtp53 Infection Of mentioning

confidence: 92%

“…Using SSCP (single-strand conformation polymorphism) analysis and DNA sequencing, we have shown that while MCF7 has a wt p53 gene, both TNF resistant sublines (1001 and MCF7/Adr) derived from the parental MCF7 cells exhibit mutant p53. This includes in 1001 clone a point mutation P280K, known to be located in the p53 DNA-interaction site and in MCF7/Adr cells a point mutation at the splicing acceptor site of the upstream border of exon 5 resulting in a 21 pb deletion (Cai et al, 1997b). To further con®rm the implication of p53 in TNF-induced cell death, we transferred wt p53 in TNF resistant cells expressing mutant p53 using an adenoviral vector.…”

Section: Functional Wt P53 Expression Following Adwtp53 Infection Of mentioning

confidence: 99%

“…Recently, we have provided evidence for the existence of an association between the resistance of human breast adenocarcinoma cell line MCF7 to the cytotoxic action of TNF and the loss of p53 function (Cai et al, 1997b). p53 is the most frequently mutated gene in human cancers (Hainaut et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Functional Wt P53 Expression Following Adwtp53 Infection Of mentioning

confidence: 92%

Section: Functional Wt P53 Expression Following Adwtp53 Infection Of mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, we have shown that the resistance of human breast adenocarcinoma cell line MCF7 to the cytotoxic action of TNF was associated with the loss of p53 function. 30 Moreover, we have demonstrated that the transfer of wtp53 using an adenoviral vector ( Adwtp53) reestablishes TNF sensitivity in TNF -resistant cells. 31 In the present study, we investigated the mechanisms of the p53 -mediated restoration of TNF sensitivity.…”

mentioning

confidence: 99%

Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: Role of caspase-8 and mitochondria

et al. 2002

Self Cite

View full text Add to dashboard Cite

In the present study, we have investigated the mechanisms by which the restoration of wild -type ( wt ) p53 functions in p53 mutant cells increases their susceptibility to the cytotoxic action of tumor necrosis factor ( TNF ). Our data indicate that the resistance of p53 -mutated cl.1001 cells to TNF -induced cell death was not due to a defect in the expression of TRADD and FADD, yet correlated with a reduced caspase -8 activation as well as a deficient mitochondrial membrane permeabilization. Moreover, cl.1001 cells failed to translocate the mitochondrial AIF and cytochrome c to the nucleus and to the cytosol, respectively, in response to TNF. Sensitization of these cells, following infection with a recombinant adenovirus encoding wtp53, to TNF -induced cytotoxicity resulted in the restoration of caspase -8 cleavage and the reestablishment of mitochondrial signs of apoptosis. These findings suggest that the crosstalk between p53 and TNF -induced cell death depends on mitochondria and 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.

show abstract

Cytotoxic sensitivity to tumor necrosis factor-? in PC3 and LNCaP prostatic cancer cells is regulated by extracellular levels of SGP-2 (clusterin)

et al. 1999

View full text Add to dashboard Cite

BACKGROUND SGP‐2 is a ubiquitous secreted glycoprotein that prevents cellular apoptosis. This study was carried out to determine the extracellular action of SGP‐2 in a model of tumor necrosis factor‐α (TNF)‐induced cytotoxicity using two human prostatic cancer lines, LNCaP and PC3. These two lines were selected because LNCaP cells are highly sensitive to the cytotoxic effect of TNF, while PC3 cells are resistant to TNF at 24 hr. METHODS Cells were cultured in the presence or absence of TNF (10 ng/ml). LNCaP cells were treated with varying concentrations of exogenous SGP‐2, while PC3 cells were treated with antisera to SGP‐2 with and without exogenous SGP‐2. Following a 24‐hr treatment, cultures were assessed by counting of cell number and by the trypan blue exclusion assay. RESULTS Western blot analysis of conditioned media revealed that PC3 secreted more SGP‐2 than did LNCaP. The sensitivity to TNF in LNCaP cells was reduced by the addition of exogenous SGP‐2. PC3 cells became sensitive to TNF when SGP‐2 antibody was added to the culture. The effect of SGP‐2 antibody on PC3 cells was reversed by the addition of exogenous SGP‐2 to the culture. CONCLUSIONS These results suggest that SGP‐2 can act as an extracellular mediator of anti‐TNF‐induced cytotoxicity. Prostate 39:87–93, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

Resistance of MCF7 human breast carcinoma cells to TNF-induced cell death is associated with loss of p53 function

Cited by 78 publications

References 40 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

Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: Role of caspase-8 and mitochondria

Cytotoxic sensitivity to tumor necrosis factor-? in PC3 and LNCaP prostatic cancer cells is regulated by extracellular levels of SGP-2 (clusterin)

Contact Info

Product

Resources

About