Regulation of bcl-2 Proto-Oncogene Expression During Normal Human Lymphocyte Proliferation

Abstract

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.

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer

“…Although the mechanism which controls the accumulation of bcl-2 protein in tumours is not known, it is likely that post-transcriptional regulation is responsible for bcl-2 expression (Reed et al, 1987).…”

Flow cytometric detection of the mitochondrial BCL‐2 protein in normal and neoplastic human lymphoid cells

“…Correlation with the Cell Cycle Previous studies have noted that activated but not resting T-and B-lymphocytes bear detectable amounts of bcl-2 mRNA, reaching maximal levels within 6 to 12 h after stimulation (28). Yet, immunohistochemical data indicate that the bcl-2 protein is mostly localized in nonproliferating (e.g., Ki-67 negative) lymphocytes (26).…”

The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT

“…Our results strongly suggest that IL-4 gives a negative signal, but additional levels of control can not be ruled out. In fact, regulation of Bcl-2 expression is also mediated by IL-6, TGF-b, retinoids, phorbol esters and some viral proteins (Hanada et al, 1993;Makover et al, 1991;Reed et al, 1987;Henderson et al, 1991).…”

“…Recent studies have described a variety of stimuli that regulate the levels of bcl-2 mRNA or proteins, such as IL-6, IL-10, INF-g transforming growth factor-b (TGF-b, some viral proteins, retinoids, nerve growth factor and phorbol esters (Hanada et al, 1993;Makover et al, 1991;Reed et al, 1987;Selvakumaran et al, 1994;Katoh et al, 1997;Cohen et al, 1997;Sekiya et al, 1997). Stimulation of human peripheral blood lymphocytes with phorbol ester or phorbol ester and IL-2 causes accumulation of Bcl-2a and b mRNA (Henderson et al, 1991).…”