Lack of HLA-class I antigens in human neuroblastoma cells: analysis of its relationship to TAP and tapasin expression.
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.
Laboratorio di Oncologia, Istituto Scientifico G. Gaslini, Genoa, Italy.
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Occhino
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Pistoia
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Ferrini
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017920:Antiporters / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016259:Genes, myc; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000032:analysis / Q000235:genetics / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D017920:Antiporters; D016326:Extracellular Matrix Proteins; D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; C071692:TAP2 protein, human; D007371:Interferon-gamma