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

被引:21
|
作者
Ameyar-Zazoua, M
Larochette, N
Dorothée, G
Daugas, E
Haddada, H
Gouloumet, V
Métivier, D
Stancou, R
Mami-Chouaib, F
Kroemer, G
Chouaib, S
机构
[1] Inst Gustave Roussy, INSERM U487, Lab Cytokines & Immunol Tumeurs Humaines, F-94805 Villejuif, France
[2] Inst Gustave Roussy, CNRS UMR1599, F-94805 Villejuif, France
[3] Inst Gustave Roussy, INSERM U362, F-94805 Villejuif, France
关键词
p53; TNF; mitochondria; caspase-8;
D O I
10.1038/sj.cgt.7700434
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:219 / 227
页数:9
相关论文
共 50 条
  • [21] Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas
    Wu, Jianyuan
    Li, Qingdi Quentin
    Zhou, Huiping
    Lu, Yinying
    Li, Jueli M.
    Ma, Yao
    Wang, Li
    Fu, Tingting
    Gong, Xingjiang
    Weintraub, Michael
    Wu, Shuangchan
    Ding, Hong
    MEDICAL ONCOLOGY, 2014, 31 (07)
  • [22] ADP-ribosylation of p53 tumor suppressor protein: Mutant but not wild-type p53 is modified
    WesierskaGadek, J
    BugajskaSchretter, A
    Cerni, C
    JOURNAL OF CELLULAR BIOCHEMISTRY, 1996, 62 (01) : 90 - 101
  • [23] WILD-TYPE P53 SUPPRESSES GROWTH OF HUMAN PROSTATE-CANCER CELLS CONTAINING MUTANT P53 ALLELES
    ISAACS, WB
    CARTER, BS
    EWING, CM
    CANCER RESEARCH, 1991, 51 (17) : 4716 - 4720
  • [24] WILD-TYPE P53 SUPPRESSES THE MALIGNANT PHENOTYPE IN BREAST-CANCER CELLS CONTAINING MUTANT P53 ALLELES
    RUNNEBAUM, IB
    YEE, JK
    KIEBACK, DG
    SUKUMAR, S
    FRIEDMANN, T
    ANTICANCER RESEARCH, 1994, 14 (3A) : 1137 - 1144
  • [25] Chaperoning of Mutant p53 Protein by Wild-type p53 Protein Causes Hypoxic Tumor Regression
    Gogna, Rajan
    Madan, Esha
    Kuppusamy, Periannan
    Pati, Uttam
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (04) : 2907 - 2914
  • [26] Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas
    Jianyuan Wu
    Qingdi Quentin Li
    Huiping Zhou
    Yinying Lu
    Jueli M. Li
    Yao Ma
    Li Wang
    Tingting Fu
    Xingjiang Gong
    Michael Weintraub
    Shuangchan Wu
    Hong Ding
    Medical Oncology, 2014, 31
  • [27] p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients
    Jean-Christophe Bourdon
    Marie P Khoury
    Alexandra Diot
    Lee Baker
    Kenneth Fernandes
    Mustapha Aoubala
    Philip Quinlan
    Colin A Purdie
    Lee B Jordan
    Anne-Catherine Prats
    David P Lane
    Alastair M Thompson
    Breast Cancer Research, 13
  • [28] p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients
    Bourdon, Jean-Christophe
    Khoury, Marie P.
    Diot, Alexandra
    Baker, Lee
    Fernandes, Kenneth
    Aoubala, Mustapha
    Quinlan, Philip
    Purdie, Colin A.
    Jordan, Lee B.
    Prats, Anne-Catherine
    Lane, David P.
    Thompson, Alastair M.
    BREAST CANCER RESEARCH, 2011, 13 (01):
  • [29] Effects of adenoviral wild-type p53 gene transfer in p53 -mutated lymphoma cells
    Peter Buttgereit
    Frank Schakowski
    Angela Märten
    Karsten Brand
    Sabine Renoth
    Carsten Ziske
    Björn Schöttker
    Oliver Ebert
    Roland Schroers
    Ingo GH Schmidt-Wolf
    Cancer Gene Therapy, 2001, 8 : 430 - 439
  • [30] Wild type and mutant p53 functions
    Lozano, Guillermina
    CANCER SCIENCE, 2022, 113 : 1227 - 1227