Myc
In the 80s, we discovered that chromosome translocations in both human Burkitt lymphomas and mouse plasmacytomas link an immunoglobulin gene to the myc proto-oncogene (Adams et al PNAS 1983). Using mice bearing a myc transgene expressed under the control the Ig heavy chain gene enhancer Eï, we went on to directly demonstrate that constitutive myc expression during B lymphopoiesis is highly oncogenic (Adams et al Nature 1985). Exploration of the preneoplastic state revealed that myc had directly induced hyperproliferation and retarded B lymphoid differentiation, but full-fledged malignancy relied on somatic mutations in rare myc-driven cells (Langdon et al Cell 1986). The Eï-myc transgenic mice have proved to be an invaluable tool for cancer researchers around the world.
More recently, we have utilized a vector having regulatory sequences from the vav gene to explore the consequences of pan-haemopoietic expression of myc. The vavP vector directs transgene expression in every nucleated haemopoietic cell type we have examined, including both differentiated and progenitor cells. Intriguingly, we found that both the kinetics and nature of the malignancy were markedly influenced by the level of Myc expression. Aggressive T-cell lymphomas rapidly overwhelm mice expressing high levels of the VavP-myc gene, whereas late-onset monocytic tumors predominate in lines with lower expression (Smith et al Oncogene 2005, Blood 2006). In collaboration with Dr Peter Hurlin (Oregon Health & Science University), we are currently evaluating the tumorigenic impact of loss of the Myc antagonist Mnt (Campbell, Scott and Cory, unpublished).