論文

査読有り
2003年4月

Role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells

INTERNATIONAL JOURNAL OF CANCER
  • Y Tomita
  • ,
  • Bilim, V
  • ,
  • N Hara
  • ,
  • T Kasahara
  • ,
  • K Takahashi

104
4
開始ページ
400
終了ページ
408
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/ijc.10956
出版者・発行元
WILEY-LISS

Caspases exist as zymogens, and are activated by various extracellular stimuli, leading to apoptosis. One such stimulus is Fas/CD95, a member of the tumor necrosis factor receptor family, providing one means of cytotoxic T lymphocyte (CTL)-mediated cell lysis. Clinical evidence has shown that administration of cytokine leads to regression in selected patients with renal cell carcinomas (RCCs). Interferon-gamma (IFN-gamma) indicates its contribution to anti-tumor activity of immune cells. IFN-gamma elicits its effect through the transcription factor signal transducer and activator of transcription-1 (STAT-1), and through interferon regulatory factor-1 (IRF-1), one of the target genes of STAT-1. Our previous study demonstrated an increase in the susceptibility of ACHN cells, established from RCC, to Fas-mediated apoptosis by IFN-gamma, and the inhibition of this effect by the caspase-3 and -7 inhibitor, DEVD-CHO. We demonstrated the following phenomena in IFN-gamma-treated ACHN cells: 1) enhanced transcription of caspase-1, 3 and 7 m RNAs without any change in cleavage of their substrates; 2) increased cleavage DEVD (specific for caspase-3 and 7), but not YVAD (for caspase-1) or DMQD (for caspase-3), after anti-Fas/CD95 MAb treatment; 3) activation of the STAT-1 and IRF-1 pathway; and 4) partial abrogation of the IFN-gamma-induced increase in Fas-mediated apoptosis by antisense IRF-1 oligodeoxynucleotide. These results suggest that IRF-1 plays a pivotal role in the IFN-gamma-mediated-enhancement of Fas/CD95-mediated apoptosis, through regulation of DEVD-CHO-sensitive caspases, most likely caspase-7. (C) 2003 Wiley-Liss, Inc.

リンク情報
DOI
https://doi.org/10.1002/ijc.10956
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/12584735
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000181566800002&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/ijc.10956
  • ISSN : 0020-7136
  • PubMed ID : 12584735
  • Web of Science ID : WOS:000181566800002

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