Abstract
In neuroblastoma, N-myc suppresses the expression of major histocompatibility complex (MHC) Class I antigens by reducing the binding of a nuclear factor to the enhancer-A element in the MHC Class I gene promoter. We show here that the p50 subunit of NF-kappa B is part of this complex and that expression of p50 mRNA is suppressed by N-myc. Transfection of a p50 expression vector in neuroblastoma cells that express N-myc at a high level leads to restoration of factor binding to the MHC Class I gene enhancer, restores enhancer activity and leads to re-expression of MHC Class I antigens at the cell surface. These data indicate that the p50 subunit of NF-kappa B is involved in the regulation of MHC Class I antigen expression and that N-myc down-regulates MHC Class I gene expression primarily through suppression of p50 expression.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Base Sequence
-
Binding Sites
-
Blotting, Northern
-
Chloramphenicol O-Acetyltransferase / genetics
-
Chloramphenicol O-Acetyltransferase / metabolism
-
Enhancer Elements, Genetic
-
Fluorescent Antibody Technique
-
Gene Expression Regulation, Neoplastic
-
Genes, MHC Class I*
-
Genes, myc*
-
HeLa Cells
-
Histocompatibility Antigens Class I / analysis
-
Histocompatibility Antigens Class I / genetics
-
Humans
-
Macromolecular Substances
-
Molecular Sequence Data
-
NF-kappa B / genetics
-
NF-kappa B / metabolism*
-
Neuroblastoma
-
Oligodeoxyribonucleotides
-
Rats
-
Recombinant Proteins / metabolism
-
Suppression, Genetic*
-
Transfection
-
Tumor Cells, Cultured
Substances
-
Histocompatibility Antigens Class I
-
Macromolecular Substances
-
NF-kappa B
-
Oligodeoxyribonucleotides
-
Recombinant Proteins
-
Chloramphenicol O-Acetyltransferase