Novel biological approaches for detecting oncogenic cooperation with Bcl-2

grantor: University of TorontoSeventy to ninety percent of follicular lymphomas possess a characteristic t(14;18) translocation resulting in deregulated expression of the proto-oncogene Bcl-2. Overexpression of Bcl-2 alone is not sufficient to cause full cellular transformation. According to the "two-hit" hypothesis, cellular transformation in lymphoma occurs when, at least, one other genetic alteration cooperates with deregulation of Bcl-2. c-' myc' has been suggested to fulfill this role. Using a non-transformed, overexpressing Bcl-2 only, and a transformed, overexpressing Bcl-2, c-'myc' and possessing mutant p53, cell line we developed various assays in which we can detect oncogenic cooperation with Bcl-2. When we used a transformed cell line that only overexpresses Bcl-2 and c-'myc' we were not able to detect oncogenic cooperation. Our results suggest that co-overexpression of Bcl-2 and c-'myc' is not sufficient to cause full cellular transformation and that additional cooperative genetic lesions must be acquired.M.Sc