Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-11-2
pubmed:abstractText
Several laboratories have attempted with little success to induce Fas-mediated apoptosis in prostate cancer (PCa) cells, using different external Fas agonists, i.e., anti-Fas antibodies and membrane-bound FasL. The present study confirms these earlier results using the anti-Fas antibody CH-11 in five human PCa cell lines (PPC-1, LNCaP, PC-3, TSU-Pr1, and DU145). However, intracellular murine FasL expression induced Fas-mediated apoptosis in all CH-11-resistant cell lines. Adenovirus (AdGFPFasL(TET)) was used to deliver a Murine FasL-GFP fusion gene into human PCa cells resulting in 70-98% apoptosis at 48 h as determined by the MTS assay. DU145 and PPC-1 cells treated with AdGFPFasL(TET) stained positive for the TUNEL assay, indicating that cell death was via apoptosis. Using immunofluorescent microscopy, Fas and GFPFasL colocalized to the same intracellular compartment. The anti-Fas neutralizing antibody ZB-4 was unable to block AdGFPFasL(TET)-mediated cell death, suggesting that intracellular FasL may ligate Fas within the Golgi and/or endoplasmic reticulum. This is the first evidence suggesting that these two molecules interact prior to cell surface presentation. Collectively, these findings indicate that intracellular GFPFasL expression is superior to CH-11 at inducing Fas-mediated apoptosis in human PCa cells and may allow use of AdGFPFasL(TET) for PCa gene therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
348-58
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11020350-Adenoviridae, pubmed-meshheading:11020350-Antibodies, Monoclonal, pubmed-meshheading:11020350-Antigens, CD95, pubmed-meshheading:11020350-Apoptosis, pubmed-meshheading:11020350-Cytotoxicity, Immunologic, pubmed-meshheading:11020350-Fas Ligand Protein, pubmed-meshheading:11020350-Flow Cytometry, pubmed-meshheading:11020350-Gene Expression, pubmed-meshheading:11020350-Gene Therapy, pubmed-meshheading:11020350-Genetic Vectors, pubmed-meshheading:11020350-Green Fluorescent Proteins, pubmed-meshheading:11020350-Humans, pubmed-meshheading:11020350-Luminescent Proteins, pubmed-meshheading:11020350-Male, pubmed-meshheading:11020350-Membrane Glycoproteins, pubmed-meshheading:11020350-Microscopy, Confocal, pubmed-meshheading:11020350-Prostatic Neoplasms, pubmed-meshheading:11020350-Recombinant Fusion Proteins, pubmed-meshheading:11020350-Transduction, Genetic, pubmed-meshheading:11020350-Transfection, pubmed-meshheading:11020350-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Intracellular Fas ligand expression causes Fas-mediated apoptosis in human prostate cancer cells resistant to monoclonal antibody-induced apoptosis.
pubmed:affiliation
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't