The goal of this research is to understand the activation of cellular oncogenes by chromosomal translocation, with particular emphasis on the c-myc oncogene in mouse plasmacytomas. Previous work from this laboratory has demonstrated that the first c-myc intron is transcriptionally activated by translocation and that constitutively expressed c-myc genes induce immortalized fibroblast lines to become transformed (tumorigenic). Studies will continue to explore the mechanism by which c-myc is transcribed after translocation, using gene transfer of breakpoint-linked marker genes into plasmacytoma cells. The influence of c-myc activation on primary B cells will be studied by injection of spleen or bone marrow cells with a c-myc retrovirus. These experiments will attempt to determine if c-myc activation is sufficient either to transform primary cells, to extend their growth potential, or to reduce their dependence on exogenous growth factors. We will also test the stability of c-myc mRNAs that are produced before and after translocation. We suspect that the removal of the untranslated first exon of the c-myc gene may extend the mRNA half-life and thus produce more c-myc protein with only a low rate of transcription. Ultimately, we hope to examine other types of tumors for DNA rearrangements that affect cellular oncogenes and contribute to neoplastic transformation. (M)
| Sheppard, R D; Samant, S A; Rosenberg, M et al. (1998) Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors. Oncogene 17:2073-85 |
