Linked Life Data

8824545

Source:http://linkedlifedata.com/resource/pubmed/id/8824545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1996-11-22
pubmed:abstractText
The escape of tumor cells from immune recognition is a central problem in tumor immunology. Here, we examined the functional role of somatic beta 2-microglobulin (beta2m) gene mutations in human lung and breast cancers. Using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing, we found mutations in the beta2m gene in 2 of 110 tested lung, colon and breast tumors and tumor cell lines. No mutations were identified in 63 breast cancer tumors, in B-lymphoblastoid cell lines or normal tissues from these or other patients. In these cell lines, beta2m protein was undetectable by Western blot analysis and there was no MHC class I on their cell surface even after treatment with interferon-gamma. Transfection of these tumor cell lines with the beta2m gene, but not addition of purified beta2m protein restored MHC expression without addition of exogenous pepticles, indicating that endogenous beta2m expression is necessary for proper intracellular MHC assembly and stabilization by endogeneous pepticles. Mutation in beta2m caused cell line H2009 to be resistant to specific lysis by influenza virus-specific CTL from HLA matched donors, and transfection of the beta2m gene restored this killing. A small cell lung cancer cell line with low class I expression and with a normal beta2m genomic sequence nonetheless also demonstrated increased class I expression after transfection of the beta2m expression vector alone, indicating that the availability of beta2m may be rate limiting for MHC assembly in this line. Our results indicate that somatic mutations or selective loss of expression of the beta2m gene in human lung cancer is rare, but can cause defective MHC class I expression and function allowing these cells to escape recognition by cytotoxic T cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
756-63
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Structural and functional analysis of beta2 microglobulin abnormalities in human lung and breast cancer.
pubmed:affiliation
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, USA.
pubmed:publicationType
Journal Article