The History of cMyc

c-Myc is the cellular counterpart ofthe viral oncogene v-myc that was identified as the transforming factor in avian retroviruses, MH-2, MC29 (2), CMII and OK 10 (3). Subsequently, it was discovered that bursal B-cell lymphomas in retrovirus-infected fowl were caused by retroviral integrations in or near the c-myc proto-oncogene, which caused constitutive expression of c-myc. In some cases, these transcripts originated at the promoter in the long terminal repeat (LTR) of the retrovirus (4). In other cases, the nearby strong retroviral enhancer induced constitutive expression that originated in one of the c-myc promoters, if they were still attached to the coding region of the c-myc gene (5). Importantly, c-myc was recognized as a transformation-initiating oncogene in mammals when B-cell lymphomas in human beings [Burkitt lymphomas (6), rat immunocytomas in Louvain-strain rats (7), and mouse oil-induced BALB/c plasmacytomas (8,9)] were found to be associated with constitutive expression of c-myc mRNA and protein. In these tumors, chromosomal translocations juxtaposed the c-myc gene to a gene that encoded either the Ig heavy chain or one of the Ig light chains. In these cases, the strong enhancers on the Ig-encoding genes were responsible for a constitutive activation of transcription originating at one of the c-myc promoters. This mechanism is analogous to the enhancer-insertion model of bursal lymphomas. Finally, evidence of a c-myc-activating extrachromosomal translocation has been found in extrachromosomal elements in a murine plasmacytoma (10). In this ease, constitutive c-myc expression was initiated within the c-myc/IgH-carrying extrachromosomal elements.

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