Source:http://linkedlifedata.com/resource/pubmed/id/14729627
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
|
pubmed:dateCreated |
2004-1-19
|
pubmed:abstractText |
Because of its amplification and/or overexpression in many human tumors, the HER-2/neu proto-oncogene represents an attractive target for T-cell-mediated vaccination strategies. However, overexpression of oncogenes is often associated with defective expression of components of the MHC class I antigen-processing machinery (APM), thereby resulting in an immune escape phenotype of oncogene-transformed cells. To determine whether HER-2/neu influences the MHC class I antigen-processing pathway, the expression pattern of different APM components was examined in murine in vitro models of constitutive and tetracycline-controlled HER-2/neu expression. In comparison with HER-2/neu(-) control cells, HER-2/neu(+) fibroblasts exhibit reduced levels of MHC class I surface antigens that were associated with impaired expression and/or function of the peptide transporter associated with antigen processing, the proteasome subunits low molecular weight protein 2 and low molecular weight protein 10, the proteasome activators PA28alpha and PA28beta, and tapasin. These APM abnormalities resulted in reduced sensitivity to lysis by CTLs. The HER-2/neu-mediated immune escape phenotype could be corrected by IFN-gamma treatment. The clinical relevance of this finding was supported by an inverse correlation between HER-2/neu and the peptide transporter associated with antigen-processing protein expression as determined by immunhistochemical analysis of a series of HER-2/neu(-) and HER-2/neu(+) breast cancer specimens. Thus, a functional link between deficient APM component expression and HER-2/neu overexpression is proposed that might influence the design of HER-2/neu-targeted T-cell-based immunotherapeutic strategies.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
0008-5472
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
64
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
215-20
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:14729627-3T3 Cells,
pubmed-meshheading:14729627-Animals,
pubmed-meshheading:14729627-Gene Expression Regulation,
pubmed-meshheading:14729627-Histocompatibility Antigens Class I,
pubmed-meshheading:14729627-Immunotherapy,
pubmed-meshheading:14729627-Mice,
pubmed-meshheading:14729627-Mice, Knockout,
pubmed-meshheading:14729627-Receptor, erbB-2,
pubmed-meshheading:14729627-T-Lymphocytes,
pubmed-meshheading:14729627-Transfection
|
pubmed:year |
2004
|
pubmed:articleTitle |
HER-2/neu-mediated regulation of components of the MHC class I antigen-processing pathway.
|
pubmed:affiliation |
Third Department of Internal Medicine and Pathology, Johannes Gutenberg-University, Mainz, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|