These studies focus on regulation of the murine c-myc oncogene gene, the cellular homologue of the MC29 virus transforming gene. There is evidence that c-myc expression is highly regulated in normal cells where its induction correlates with an early phase of mitogen activation and that alterations in c-myc expresion can play a causal role in malignant transformation. Accordingly, elucidation of the regulation, as well as the function, of the c-myc gene appears to be a key element for understanding normal growth control and malignant transformation. The proposed experiments will characterize the regulation of both normal c-myc gene expression and the aberrant c-myc gene expression which occurs after translocation of the c-myc gene in murine plasmacytomas. These studies are divided into three parts. The first part centers on transcriptional regulation of the normal c-myc gene. The studies will show if c-myc repression occurs when cellular levels of myc protein are elevated and if myc protein autoregulates the c-myc gene. The c-myc gene region required for its repression will be mapped. The ability of 1,25 dihydroxy vitamin D3 to repress c-myc transcription will also be confirmed and studied. In the second part of the study the mechanism(s) responsible for activating transcription of translocated c-myc genes from cryptic promoters in murine plasmacytomas will be characterized. These experiments will demonstrate if DNA sequences from the immunoglobulin region are necessary for c-myc activation; if so, the region will be mapped and the tissue specificity of the activation will be explored. In the final portion of the work, steady state levels and stability of c-myc mRNA and myc protein in quiescent normal cells, mitogen induced cells and plasmacytoma tumors will be compared. (X)