DNA binding of regulatory factors interacting with MHC-class-I gene enhancer correlates with MHC-class-I transcriptional level in class-I-defective cell lines.
Tumor cells frequently show a lack of surface class-I major histocompatibility complex (MHC) antigen expression. These molecules are key recognition structures for immune rejection of tumor cells and their absence at the surface of tumor cells could favor the progression of tumors. We have analyzed the transcriptional mechanisms that could lead to suppression of MHC-class-I expression in human tumor cell K562. The expression of MHC-class-I genes is highly controlled by regulatory factors interacting with an enhancer sequence upstream of MHC-class-I genes. In this report we show that DNA binding activity of 2 regulatory factors, KBFI and NF-kappa B, known to be essential for constitutive expression of MHC-class-I genes, is deficient in nuclear extracts from K562 cells. Induction of class-I gene expression at the surface of tumor cells by interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) shows that TNF-alpha can act in synergy with IFN-gamma to induce DNA binding of both factors NF-kappa B and KBFI to the class-I gene enhancer and that this induction of transcriptional factors is correlated with enhancement of MHC-class-I mRNA transcription and cell-surface antigen expression.
Blanchet
O
O
INSERM U93, Centre Hayem, Hôpital Saint-Louis, Paris, France.
Bourge
J F
JF
Zinszner
H
H
Tatari
Z
Z
Degos
L
L
Paul
P
P
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D006367:HeLa Cells / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma