Abstract
Adenovirus type 12 (Ad12)-transformed baby rat kidney (BRK) cells are oncogenic in syngeneic immunocompetent rats in contrast to adenovirus type 5 (Ad5)-transformed BRK cells, which are not oncogenic in these animals. A significant factor contributing to the difference in oncogenicity may be the low levels of major histocompatibility complex (MHC) class I membrane expression in Ad12-transformed BRK cells as compared with those in Ad5-transformed BRK cells, which presumably results in escape from killing by cytotoxic T lymphocytes. Here we show that, in addition to the decreased levels of expression of the MHC class I heavy chain and the peptide transporter Tap-2, the expression levels of the chaperone Tapasin and the immunoproteasome components MECL-1, PA28-alpha, and PA28-beta also are much lower in Ad12- than in Ad5-transformed BRK cells. The low expression levels of these proteins may contribute to the escape from killing by cytotoxic T lymphocytes, because the generation of optimal peptides and loading of these peptides on MHC class I require these components. Increased levels of phosphorylated signal transducer and activator of transcription-1 protein and expression of IFN regulatory factor-7 were found in Ad5- versus Ad12-transformed BRK cells. Therefore, the critical alteration leading to the plethora of differences may be an interferon (-related) effect.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Adenoviridae / genetics*
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Adenoviridae / metabolism
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Animals
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Animals, Newborn
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Antiporters / genetics
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Antiporters / metabolism*
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Cell Cycle Proteins
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Cell Line
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Cell Transformation, Viral*
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Culture Media, Conditioned
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Cysteine Endopeptidases / immunology*
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Cysteine Endopeptidases / metabolism
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DNA-Binding Proteins / metabolism
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Flow Cytometry
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Gene Expression Regulation*
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Genes, MHC Class I
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Histocompatibility Antigens / genetics
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Histocompatibility Antigens / metabolism
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism*
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Immunoglobulins / genetics
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Immunoglobulins / metabolism*
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Interferon-gamma / metabolism
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Kidney / cytology
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Membrane Transport Proteins
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism*
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Multienzyme Complexes / immunology*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Oncogenes
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Phosphorylation
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Proteasome Endopeptidase Complex
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Protein Subunits / metabolism
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Proteins / metabolism
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Rats
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STAT1 Transcription Factor
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Trans-Activators / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters
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Antiporters
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Cell Cycle Proteins
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Culture Media, Conditioned
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DNA-Binding Proteins
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Histocompatibility Antigens
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Histocompatibility Antigens Class I
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Immunoglobulins
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Membrane Transport Proteins
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Molecular Chaperones
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Multienzyme Complexes
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NF-kappa B
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Protein Subunits
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Proteins
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Psme1 protein, rat
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Psme2 protein, rat
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STAT1 Transcription Factor
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Tap2 protein, rat
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Trans-Activators
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Tumor Necrosis Factor-alpha
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histocompatibility antigens RT, rat
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tapasin
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TAP2 protein, human
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Interferon-gamma
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Psmb10 protein, rat