Linked Life Data

11683408

Source:http://linkedlifedata.com/resource/pubmed/id/11683408

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 15
pubmed:dateCreated
2001-10-30
pubmed:abstractText
In this study we investigated the functional role of FAP-1 as a potential inhibitor of CD95 (Fas, APO-1)-mediated apoptosis in pancreatic cancer cells. Stable transfection of the CD95-sensitive, FAP-1-negative cell line Capan-1 with an FAP-1 cDNA resulted in a strongly decreased sensitivity to CD95-induced apoptosis, as measured by DNA fragmentation and caspase-3 activity. Inhibition of cellular protein tyrosine phosphatases with orthovanadate dose-dependently increased CD95-induced apoptosis in CD95-resistant FAP-1-positive Panc89 and Capan-1-FAP-1 cells almost to the level seen in wild-type Capan-1 cells. Blocking the CD95/FAP-1 interaction in Panc89 cells by cytoplasmic microinjection of a synthetic tripeptide mimicking the C terminus of CD95 resulted in a mean 5.5-fold increase in apoptosis compared to cells that received a control peptide. Using confocal laser scanning microscopy we show that in Panc89 cells FAP-1 is mainly associated with the Golgi complex and with peripheral vesicles. FAP-1 displayed enhanced colocalization with CD95 upon CD95 stimulation in the Golgi complex but not in surface-associated vesicles. This correlated with a decrease in plasma membrane staining for CD95 as determined by FACS analysis. Inhibition of Golgi anterograde transport by brefeldin A abolished the anti-CD95-induced colocalization of FAP-1 and CD95 as well as the decrease in cell-surface-associated CD95. Finally, we demonstrate by immunohistochemistry that FAP-1 is strongly expressed in tumor cells from pancreatic carcinoma tissues. Taken together, these results show that FAP-1 can protect pancreatic carcinoma cells from CD95-mediated apoptosis, probably by preventing anti-CD95-induced translocation of CD95 from intracellular stores to the cell surface.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2735-46
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11683408-Adenocarcinoma, pubmed-meshheading:11683408-Antigens, CD95, pubmed-meshheading:11683408-Apoptosis, pubmed-meshheading:11683408-Brefeldin A, pubmed-meshheading:11683408-Carrier Proteins, pubmed-meshheading:11683408-Cytoplasmic Vesicles, pubmed-meshheading:11683408-Fluorescent Antibody Technique, pubmed-meshheading:11683408-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11683408-Golgi Apparatus, pubmed-meshheading:11683408-Humans, pubmed-meshheading:11683408-Jurkat Cells, pubmed-meshheading:11683408-Pancreatic Neoplasms, pubmed-meshheading:11683408-Peptide Fragments, pubmed-meshheading:11683408-Protein Synthesis Inhibitors, pubmed-meshheading:11683408-Protein Tyrosine Phosphatase, Non-Receptor Type 13, pubmed-meshheading:11683408-Protein Tyrosine Phosphatases
pubmed:year
2001
pubmed:articleTitle
FAP-1 in pancreatic cancer cells: functional and mechanistic studies on its inhibitory role in CD95-mediated apoptosis.
pubmed:affiliation
Clinic for General Surgery and Thoracic Surgery, Christian-Albrechts-University, Kiel, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't