ORGANIZATION AND CONTROL OF GENETIC MATERIAL IN PLASMACYTOMAS

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It is the long range purpose of this project to study the control mechanisms important in regulating cell growth, neoplastic transformation, and protein synthesis in normal and malignant cells of the immune system. To this end we are studying the structure of the proto-oncogenes in normal and tumor tissues from mouse and man and the expression of these oncogenes as mRNAs and proteins in mouse plasmacytomas and mouse and human myeloid and lymphoid tumors. In addition, we are investigating what role Abelson and Moloney leukemia viruses as well as recombinant viral constructs play in the induction of mouse tumors and alteration of their cellular oncogenes. We have discovered that Moloney leukemia viruses frequently insert themselves as proviruses in either the 5' end or 3' end of the mouse c-myb locus in certain myeloid tumors. We have isolated cDNA clones of murine and human c-myb transcripts from myeloid and lymphoid tumors and are characterizing these clones and the genes encoding c-myb in both these species. We have found that recombinant viruses containing mouse c-myc genes induce plasmacytomas or myeloid tumors in pristane-primed BALB/c mice; the nature of the viral oncogene determines the tumor type. Studies on these and other plasmacytomas indicate that expression of myc is regulated at a number of different metabolic sites. We have found that the very high levels of c-myc RNA in two of these tumors result from a combination of increased transcription of the c-myc gene and a stabilization of the c-myc RNA transcripts. We are studying whether these tumors with high c-myc RNA levels can constantly produce super abundant amounts of myc protein or if myc RNAs are subjected to translational control mechanisms. We are also studying how much translational controls operate in immunoglobulin synthesis in B lymphocytes.