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2008 | 55 | 4 | 741-748
Tytuł artykułu

TNFalpha-induced activation of NFkappaB protects against UV-induced apoptosis specifically in p53-proficient cells

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Języki publikacji
The signaling pathways that depend on p53 or NFκB transcription factors are essential components of cellular responses to stress. In general, p53 is involved in either activation of cell cycle arrest or induction of apoptosis, while NFκB exerts mostly anti-apoptotic functions; both regulatory pathways apparently interfere with each other. Here we aimed to analyze the effects of NFκB activation on DNA damage-induced apoptosis, either p53-dependent or p53-independent, in a set of human cell lines. Four cell lines, HCT116 and RKO colon carcinoma, NCI-H1299 lung carcinoma and HL60 myeloblastoma, each of them in two congenic variants either containing or lacking transcriptionally competent p53, were used. Cells were incubated with TNFα cytokine to activate NFκB and then treated with ultraviolet or ionizing radiation to induce apoptosis, which was assessed by measurement of the sub-G1 cell fraction. We observed that treatment with TNFα resulted in a significant reduction in the frequency of apoptotic cells in UV-irradiated p53-proficient lines (with exception of the UV-resistant NCI-H1299 cells). This anti-apoptotic effect was lost when cells were pretreated with parthenolide, an inhibitor of NFκB activation. In marked contrast, TNFα-pretreatment of p53-deficient lines resulted in an increased frequency of apoptotic cells after UV irradiation (with exception of HL60 cells). Such anti- and pro-apoptotic influence of TNFα was less obvious in cells treated with ionizing radiation. The data clearly indicates functional interference of both signaling pathways upon the damage-induced apoptotic response, yet the observed effects are both cell type- and stimulus-specific.
Opis fizyczny
  • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 44, Gliwice, Poland
  • Aleyasin H, Cregan SP, Iyirhiaro G, O'Hare MJ, Callaghan SM, Slack RS, Park DS (2004) Nuclear factor-(κ)B modulates the p53 response in neurons exposed to DNA damage. J Neurosci 24:2963-2973.
  • Ameyar M, Shatrov V, Bouquet C, Capoulade C, Cai Z, Stancou R, Badie C, Haddada H, Chouaib S (1999) 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. Oncogene 18:5464-5472.
  • Ameyar-Zazoua M, Larochette N, Dorothee G, Daugas E, Haddada H, Gouloumet V, Metivier D, Stancou R, Mami-Chouaib F, Kroemer G, Chouaib S (2002) Wild-type p53 induced sensitization of mutant p53 TNF-resistant cells: role of caspase-8 and mitochondria. Cancer Gene Ther 9:219-227.
  • Baker SJ, Reddy EP (1998) Modulation of life and death by the TNF receptor superfamily. Oncogene 17:3261-3270.
  • Beg AA, Baltimore D (1996) An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274:782-784.
  • Bentires-Alj M, Dejardin E, Viatour P, Van Lint C, Froesch B, Reed JC, Merville MP, Bours V (2001) Inhibition of the NF-κB transcription factor increases Bax expression in cancer cell lines. Oncogene 20:2805-2813.
  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282:1497-1501.
  • Burstein E, Duckett CS (2003) Dying for NF-κB? Control of cell death by transcriptional regulation of the apoptotic machinery. Curr Opin Cell Biol 15:732-737.
  • Cai Z, Capoulade C, Moyret-Lalle C, Amor-Gueret M, Feunteun J, Larsen AK, Paillerets BB, Chouaib S (1997) Resistance of MCF7 human breast carcinoma cells to TNF-induced cell death is associated with loss of p53 function. Oncogene 15:2817-2826.
  • Chen JY, Funk WD, Wright WE, Shay JW, Minna JD (1993) Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences. Oncogene 8:2159-2166.
  • Delhalle S, Deregowski V, Benoit V, Merville MP, Bours V (2002) NF-κB-dependent MnSOD expression protects adenocarcinoma cells from TNF-α-induced apoptosis. Oncogene 21:3917-3924.
  • Efeyan A, Serrano M (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6:1006-1010.
  • Fujioka S, Niu J, Schmidt C, Sclabas GM, Peng B, Uwagawa T, Li Z, Evans DB, Abbruzzese JL, Chiao PJ (2004) NF-κB and AP-1 connection: mechanism of NF-κB-dependent regulation of AP-1 activity. Mol Cell Biol 24:7806-7819.
  • Hellin AC, Calmant P, Gielen J, Bours V, Merville MP (1998) Nuclear factor-κB-dependent regulation of p53 gene expression induced by daunomycin genotoxic drug. Oncogene 16:1187-1195.
  • Kessis TD, Slebos RJ, Nelson WG, Kastan MB, Plunkett BS, Han SM, Lorincz AT, Hedrick L, Cho KR (1993) Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc Natl Acad Sci USA 90:3988-3992.
  • Levesque AA, Eastman A (2007) p53-based cancer therapies: Is defective p53 the Achilles heel of the tumor? Carcinogenesis 28:13-20.
  • Morgan M, Thorburn J, Pandolfi PP, Thorburn A (2002) Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms. J Cell Biol 157:975-984.
  • Perkins ND (2004) Regulation of NF-κB by atypical activators and tumour suppressors. Biochem Soc Trans 32 (Pt 6): 936-939.
  • Rocha S, Martin AM, Meek DW, Perkins ND (2003) p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-κB subunit with histone deacetylase 1. Mol Cell Biol 23:4713-4427.
  • Rodier F, Campisi J, Bhaumik D (2007) Two faces of p53: aging and tumor suppression. Nucleic Acids Res 35:7475-7484.
  • Rokhlin OW, Guseva N, Tagiyev A, Knudson CM, Cohen MB (2001) Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis. Oncogene 20:2836-2843.
  • Saile B, Matthes N, El Armouche H, Neubauer K, Ramadori G (2001) The bcl, NFκB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-β or TNF-α on activated hepatic stellate cells. Eur J Cell Biol 80:554-561.
  • Schumm K, Rocha S, Caamano J, Perkins ND (2006) Regulation of p53 tumour suppressor target gene expression by the p52 NF-κB subunit. EMBO J 25:4820-4832.
  • Tergaonkar V, Pando M, Vafa O, Wahl G, Verma I (2002) p53 stabilization is decreased upon NFκB activation: a role for NFκB in acquisition of resistance to chemotherapy. Cancer Cell 1:493-503.
  • Tian B, Brasier AR (2003) Identification of a nuclear factor κB-dependent gene network. Recent Prog Horm Res 58:95-130.
  • Webster GA, Perkins ND (1999) Transcriptional cross talk between NF-κB and p53. Mol Cell Biol 19:3485-3495.
  • Wolf D, Rotter V (1985) Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc Natl Acad Sci USA 82:790-794.
  • Yan B, Chen G, Saigal K, Yang X, Jensen ST, Van Waes C, Stoeckert CJ, Chen Z (2008) Systems biology-defined NF-κB regulons, interacting signal pathways and networks are implicated in the malignant phenotype of head and neck cancer cell lines differing in p53 status. Genome Biol 9:R53.
  • Zhang S, Lin ZN, Yang CF, Shi X, Ong CN, Shen HM (2004) Suppressed NF-κB and sustained JNK activation contribute to the sensitization effect of parthenolide to TNF- α-induced apoptosis in human cancer cells.Carcinogenesis 25:2191-2199.
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