THE FUNCTIONAL BASIS OF C-MYC AND BCL-2 COMPLEMENTATION DURING MULTISTEP LYMPHOMAGENESIS IN-VIVO

Oncogenes are known to be deregulated by chromosomal translocations oc curring at high frequency in specific malignancies. Among the most wel l characterized of these are c-myc, associated with the t(8;14) in Bur kitt's lymphomas, and bcl-2, associated with the t(14;18) in follicula r lymphomas. In addition to their role in regulating rates of prolifer ation, it is known that oncogenes and tumor suppressor genes can also regulate rates of apoptotic cell death. The contribution of c-myc and bcl-2 to the regulation of cell death during lymphomagenesis in vivo i s assessed using bcl-2-Ig and E mu-myc transgenic mice and bcl-2/myc h ybrid transgenic mice. Translocations between the endogenous c-myc gen e and immunoglobulin loci, e.g., t(12;15), are common in lymphomas ari sing in the bcl-2-Ig mice. Furthermore, bcl-2/c-myc double transgenic mice exhibit accelerated lymphomagenesis, indicating cooperation betwe en these two oncogenes. Genetic complementation of c-myc and bcl-2 dur ing lymphomagenesis resulted from the suppression of c-myc-associated apoptosis. Other genes are likely involved in regulating cell death du ring multistep lymphomagenesis. (C) 1995 Academic Press, Inc.