Expression of normal and translocated c-myc alleles in Burkitt's lymphoma cells: evidence for different regulation.
In Burkitt's lymphoma (BL) cells the normal c-myc allele is usually silent or expressed at very low levels. Here we demonstrate that the normal c-myc allele can be induced in BL cells by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA did activate the normal c-myc alleles in Raji(P207), BL36, P3HR1, Jijoye and LY91 cells, but not in Raji(DE88), BL41, BL67, LY47 and KK124 cells. C-myc RNA derived from the normal allele appeared 6 h after treatment with TPA and showed the characteristic preferential usage of the second promoter. This induction could not be inhibited by cycloheximide. Despite the differences in c-myc induction in Raji(P207) and Raji(DE88) cells, c-fos and the early Epstein-Barr virus gene DR were induced to a similar extent and with similar kinetics by TPA. Nuclear run-on experiments suggest that the normal c-myc allele in Raji cells is activated at least in part by releasing a block to RNA elongation at the end of c-myc exon 1. Expression of the translocated c-myc alleles was also affected by TPA; however, only if cycloheximide was simultaneously present. TPA plus cycloheximide induced a rapid decrease of c-myc RNA derived from the translocated allele within 6 h, whereas cycloheximide alone led to abolition of c-myc RNA after 16-24 h. This rapid decline of c-myc RNA was observed in Raji and BL41 cells, but not in three cell lines with variant t(2;8) and t(8;22) translocations.
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Institut für Medizinische Mikrobiologie und Hygiene der Universität Freiburg, FRG.
Bornkamm
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GW
D000483:Alleles; D000841:Anisomycin / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000235:genetics*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D000841:Anisomycin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate