Linked Life Data

15302575

Source:http://linkedlifedata.com/resource/pubmed/id/15302575

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-8-10
pubmed:abstractText
Although melanocytes are devoid of the human major histocompatibility complex class II (HLA II) molecules, melanomas often display constitutive expression of these molecules, particularly HLA-DR. This constitutive expression of HLA-DR molecules is associated with tumor progression and poor prognosis but the molecular basis for this association remains poorly understood. Within the hypothesis of a role in immune escape, we analyzed the regulation of Fas-mediated apoptosis by HLA-DR signaling in the HLA-DR-positive malignant melanoma cell line A375. Our study demonstrates that engagement of HLA-DR molecules with anti-HLA-DR-specific monoclonal antibody L243 significantly reduces Fas-mediated apoptosis; DNA fragmentation and cell death were decreased by 50% and 40%, respectively. We found that while HLA-DR signaling does not affect Fas receptor expression, it significantly reduces Fas-induced activation of caspase-8 and Bid. Furthermore, inhibition studies and expression of dominant negative form of Mek-1 demonstrated that HLA-DR-mediated inhibition of caspase-8/Bid activation and apoptosis are dependent on the activation of the MAPK/Erk pathway. Together, our results provide evidence that HLA-DR signaling activates the MAPK/Erk pathway in A375 melanoma cells, which has a functional role in the resistance of these cells to Fas-mediated apoptosis. These observations underline the potential importance that HLA-DR signaling might have in melanoma immune escape and tumor progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-90
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15302575-Antibodies, pubmed-meshheading:15302575-Antigens, CD95, pubmed-meshheading:15302575-Apoptosis, pubmed-meshheading:15302575-BH3 Interacting Domain Death Agonist Protein, pubmed-meshheading:15302575-Carrier Proteins, pubmed-meshheading:15302575-Caspase 8, pubmed-meshheading:15302575-Caspases, pubmed-meshheading:15302575-Cell Line, Tumor, pubmed-meshheading:15302575-Cell Transformation, Neoplastic, pubmed-meshheading:15302575-Disease Progression, pubmed-meshheading:15302575-Down-Regulation, pubmed-meshheading:15302575-Feedback, Physiological, pubmed-meshheading:15302575-HLA-DR Antigens, pubmed-meshheading:15302575-Humans, pubmed-meshheading:15302575-MAP Kinase Signaling System, pubmed-meshheading:15302575-Melanocytes, pubmed-meshheading:15302575-Melanoma, pubmed-meshheading:15302575-Neoplasm Metastasis, pubmed-meshheading:15302575-Prognosis, pubmed-meshheading:15302575-Signal Transduction
pubmed:year
2004
pubmed:articleTitle
HLA-DR signaling inhibits Fas-mediated apoptosis in A375 melanoma cells.
pubmed:affiliation
Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, Québec, Canada G1V 4G2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't