In vitro modulation and relationship between N-myc and HLA class I RNA steady-state levels in human neuroblastoma cells.
Neuroblastoma cell lines and tumors are characterized by low HLA class I expression. The majority of neuroblastoma cell lines and a high percentage of disseminated tumors display amplification of the nuclear protooncogene N-myc. An inverse correlation between HLA class I expression and N-myc amplification and overexpression has been recently described in neuroblastomas (NBs). In this study we have shown that cytokines (recombinant gamma-interferon, recombinant alpha-tumor necrosis factor), differentiation agents (dibutyryl cyclic AMP, phorbol myristate acetate) and growth factors (nerve growth factor, epithelial growth factor) were able to influence the growth rate and surface expression of HLA class I molecules as well as of a tumor-associated antigen on 2 representative NB cell lines. Induced decreased growth rate in NB cells was not always related to decreased N-myc expression. Analysis at the mRNA level revealed that both N-myc and HLA class I RNA steady-state levels could be modulated by several substances, including recombinant gamma-interferon, phorbol myristate acetate, dibutyryl cyclic AMP, and epithelial growth factor and were not necessarily linked. An inverse correlation between N-myc and HLA mRNA levels was observed only after exposure of NB cells to recombinant alpha-tumor necrosis factor. We conclude that N-myc and HLA class I RNA steady-state levels can be modulated independently and suggest that they are not necessarily inversely regulated.
Pediatric Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
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N
Gross
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Beck
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Favre
D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D016274:Oncogene Protein p55(v-myc) / Q000096:biosynthesis*; D012313:RNA / Q000302:isolation & purification; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D009414:Nerve Growth Factors; D016274:Oncogene Protein p55(v-myc); D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D012313:RNA; D003994:Bucladesine; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate