Document Detail


Lack of FasL-mediated killing leads to in vivo tumor promotion in mouse Lewis lung cancer.
MedLine Citation:
PMID:  12766475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lewis lung carcinoma (3LL) cells were constitutively resistant to Fas-mediated apoptosis, but overexpression of Fas on 3LL cells allowed Fas-mediated apoptosis after crosslinking with agonist anti-Fas antibody (Jo2) in vitro. Surprisingly, Fas-overexpressing 3LL cells showed enhanced in vivo tumor progression, whereas no promotion of in vivo tumor growth was observed for dominant negative (DN) Fas-overexpressing 3LL transfectants in which the cytoplasmic death domain was deleted. In addition, the promotion of in vivo tumor growth by Fas-overexpression was reduced in gld (FasL-mutation) mice compared to normal mice. These data indicate that intact Fas/FasL cell signaling is required for the promotion of in vivo tumor growth by Fas overexpression in 3LL cells. In contrast to the efficient Fas-mediated killing induced in vitro by crosslinking with anti-Fas antibody, Fas-overexpressing 3LL cells were resistant in vitro to Fas-mediated apoptosis by activated T cells or transient FasL transfection. These data suggest that agonist anti-Fas antibody and natural FasL can transmit qualitatively different signals, and crosslinking of Fas with natural FasL on 3LL cells does not deliver the expected death signal. Thus, our results demonstrate that in some cases overexpression of Fas can result in a survival advantage for tumor cells in vivo.
Authors:
J-K Lee; T J Sayers; T C Back; J M Wigginton; R H Wiltrout
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  8     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-05-26     Completed Date:  2004-01-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  151-60     Citation Subset:  IM    
Affiliation:
National Genome Research Institute, National Institute of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul 122-701, Korea. cookie_jklee@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Carcinoma, Lewis Lung / pathology*
Cell Division
Cross-Linking Reagents / pharmacology
Cytoplasm / metabolism
DNA / metabolism
Disease Progression
Fas Ligand Protein
Flow Cytometry
Genetic Vectors
Interferon-gamma / metabolism
Membrane Glycoproteins / metabolism,  physiology*
Mice
Mice, Inbred C57BL
Mutation
Neoplasms / pathology
Protein Structure, Tertiary
Signal Transduction
T-Lymphocytes / metabolism
Time Factors
Transfection
Up-Regulation
Chemical
Reg. No./Substance:
0/Cross-Linking Reagents; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins; 82115-62-6/Interferon-gamma; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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