Oncogenic Potential of Bcl-2 Demonstrated by Gene Transfer

Follicular lymphoma is the most common human B-cell malignancy in the United States and Western Europe. Most of the tumours contain t(14;18) chromosome translocations involving the human bcl-2 gene. Translocation of bcl-2 sequences from chromosome 18 into the transcriptionally active immunoglobulin locus at chromosome band 14q32 in B cells deregulates bcl-2 gene expression, resulting in the accumulation of high levels of bcl-2 messenger. Human bcl-2 transcripts generate two proteins, p26 bcl-2-alpha and p22 bcl-2-beta, by virtue of alternative splice-site selection. Both proteins have in common their first 196 NH2-terminal amino acids but share little similarity with other sequences in a data bank. Although the biological and biochemical functions of bcl-2 are unknown, recent subcellular localization studies indicate that p26 bcl-2-alpha associates with cellular membranes, consistent with a stretch of hydrophobic amino acids in its carboxy terminus. The bcl-2 gene may represent a novel oncogene having no known retroviral counterpart. Here we demonstrate the oncogenic potential of bcl-2 through a gene transfer approach.