Regulation of bcl-2 proto-oncogene expression during normal human lymphocyte proliferation.

The bcl-2 and c-myc proto-oncogenes are brought into juxtaposition with the immunoglobulin heavy chain locus in particular B-cell lymphomas, resulting in high levels of constitutive accumulation of their messenger RNAs. Precisely how the products of the bcl-2 and c-myc genes contribute to tumorigenesis is unknown, but observations that c-myc expression is rapidly induced in nonneoplastic lymphocytes upon stimulation of proliferation raise the possibility that this proto-oncogene is involved in the control of normal cellular growth. In addition to c-myc, the bcl-2 proto-oncogene also was expressed in normal human B and T lymphocytes after stimulation with appropriate mitogens. Comparison of the regulation of the expression of these proto-oncogenes demonstrated marked differences and provided evidence that, in contrast to c-myc, levels of bcl-2 messenger RNA are regulated primarily through transcriptional mechanisms.