In many Balb/c mouse myeloma cell lines, the c-myc oncogene normally located on chromosome 15 has translocated to a H chain constant region locus on chromosome 12. In the majority of myelomas studied, the translocation of c-myc is to the constant region sequence (C yield) of the yield H chain """"""""non-productive"""""""" gene. The mRNA coding strand of DNA fro the c-myc gene is on the anti-sense strand for the C yield gene. While unrearranged C yield alleles are transcriptionally silent, we have shown that an excluded C yield gene element to which the c-myc oncogene has translocated is transcriptionally active. Several discrete cytoplasmic RNA species hybridizing to and yield-C probe can be detected. These are transcribed from the C yield sense strand. In a mouse myeloma MOPC 315 variant line (V-1), which has lost the yield-H chain gene, preliminary results indicate that this transcription initiates within the c-myc gene, possibly from an endogenous c-myc anti-sense promoter region(s). The site(s) of initiation of this transcription and the processing of these RNA species will be characterized by S1 mapping, cDNA cloning and sequencing. Furthermore our experiments indicate that in the murine early B-cell lymphoma WEHI 231, which contains unrearranged c-myc genes, the growth arrest induced by treatment with antibody against surface immunoglubulin or with tumor promoter, is accompanied by dramatic changes in the rate of c-myc gene transcription. Alterations in the binding of proteins to the c-myc (sense) promoter region(s) and in the structure of this DNA segment will be evaluated during the growth arrest process. Furthermore, the effect of introduction of a translocated c-myc gene into WEHI 231 cells on growth arrest will be monitored. These experiments will elucidate the mechanisms involved in normal c-myc gene regulation and evaluate the effects of the translocation on these processes. The results of these studies will help define the role of these rearrangements in the neoplastic transformation of B cells.

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National Cancer Institute (NCI)
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Boston University
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