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      Lack of HLA-class I antigens in human neuroblastoma cells: analysis of its relationship to TAP and tapasin expression.

      Tissue Antigens

      ATP-Binding Cassette Transporters, analysis, genetics, immunology, Antigens, Surface, Antineoplastic Agents, pharmacology, Antiporters, Blotting, Western, Brain Neoplasms, Extracellular Matrix Proteins, Gene Deletion, Gene Expression, drug effects, Genes, myc, Histocompatibility Antigens Class I, Humans, Immunoglobulin Heavy Chains, Immunoglobulins, Interferon-gamma, Membrane Transport Proteins, Nerve Tissue Proteins, Neuroblastoma, RNA, Messenger, Tumor Cells, Cultured, beta 2-Microglobulin

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          Abstract

          We studied the constitutive and the interferon (IFN)-gamma-induced expression of HLA class I antigen heavy chain, beta2-microglobulin (beta2m), TAP-1, TAP-2 and tapasin in a panel of eleven neuroblastoma cell lines. Surface expression of HLA class I antigens was low in eight out of eight neuroblastoma cell lines bearing MYC-N amplification and/or 1p deletion, while two out of three neuroblastoma cell lines lacking these genetic alterations showed normal expression. IFN-gamma treatment restored HLA class I antigen surface expression in all neuroblastoma cell lines. Eight out of 11 neuroblastoma cell lines did not express TAP-1 mRNA and three of them also lacked TAP-2 mRNA. beta2 m mRNA was barely detectable or absent in five neuroblastoma cell lines, while tapasin mRNA was always expressed. IFN-gamma upregulated the expression of HLA class I heavy chain, beta2 m, TAP-1, TAP-2 and tapasin, as detected at mRNA or protein level. Post-transcriptional events were involved in altered TAP-1 and beta2 m expression in one peculiar neuroblastoma cell line. These data indicate that multiple mechanisms play a role in the HLA class I antigen-deficient phenotype of human neuroblastoma.

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          11260505

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