Oncogenic potential of bcl-2 demonstrated by gene transfer

Abstract

Follicular lymphoma is the most common human B-cell malignancy in the United States and Western Europe¹. Most of the tumours contain t(14;18) chromosome translocations involving the human bcl-2 gene^2–5. 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 messenger³. Human bcl-2 transcripts generate two proteins, p26 bcl-2-α and p22 bcl-2-β, by virtue of alternative splice-site selection². Both proteins have in common their first 196 NH₂-terminal amino acids but share little similarity with other sequences in a data bank^2,4. Although the biological and biochemical functions of bcl-2 are unknown, recent subcellular localization studies indi-cate that p26 bcl-2-α associates with cellular membranes, con-sistent with a stretch of hydrophobic amino acids in its carboxy terminus^1,2,6. 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.