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Effect of interferon-γ on the susceptibility to Fas (CD95/APO-1)-mediated cell death in human hepatoma cells

Authors
 Eui-Cheol Shin  ;  Woo-Chul Shin  ;  Youjeong Choi  ;  Hoguen Kim  ;  Jeon Han Park  ;  Se Jong Kim 
Citation
 CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol.50(1) : 23-30, 2001 
Journal Title
 CANCER IMMUNOLOGY IMMUNOTHERAPY 
ISSN
 0340-7004 
Issue Date
2001
MeSH
Apoptosis/drug effects* ; Carcinoma, Hepatocellular/pathology* ; Caspase 1/genetics ; Genes, bcl-2 ; Humans ; Interferon-gamma/pharmacology* ; Liver Neoplasms/pathology* ; RNA, Messenger/analysis ; Tumor Cells, Cultured ; fas Receptor/genetics ; fas Receptor/physiology*
Keywords
IFN-γ ; Fas ; Cell death ; Hepatoma
Abstract
Many tumors, including hepatocellular carcinomas (HCCs), resist Fas-mediated cell death, which is one of the effector mechanisms in the host's anti-tumor response; however, this resistance can be abolished by interferon-γ (IFN-γ). IFN-γ may sensitize Fas-mediated cell death in several ways, but the exact mechanism in HCCs is uncertain. In this study, we thoroughly investigated the effect of IFN-γ on the susceptibility of one human normal liver cell line and 12 HCC cell lines to Fas-mediated cell death. We also investigated the effect of IFN-γ on the expression of various apoptosis-related genes such as the Fas/TNF-related genes, the bcl-2 family, and the caspase family of genes. Although most cell lines showed considerable constitutive expression of Fas, all tested cell lines resisted Fas-mediated cell death without IFN-γ. When cells were pretreated with IFN-γ, only three cell lines were made significantly susceptible to Fas-mediated cell death (SNU-354, SNU-387 and SNU-423); the other 10 cell lines were not affected. IFN-γ increased the mRNA expression of Fas, TRAIL and caspase-1, and surface Fas was also increased. The strongly sensitized cell lines (SNU-354, SNU-387 and SNU-423) showed a particularly potent increment in surface Fas after IFN-γ treatment (increase in surface Fas >1.7-fold). This result enabled us to conclude that a potent increment of surface Fas expression is a major sensitizing mechanism of IFN-γ. We conclude that IFN-γ cannot play a sensitizing role in most HCC cell lines and that IFN-γ makes HCC cells susceptible to Fas-mediated cell death through a marked up-regulation of surface Fas in some HCC cells.
Full Text
http://link.springer.com/article/10.1007/s002620000166
DOI
10.1007/s002620000166
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
Kim, Hogeun(김호근)
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142136
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