Bcl-2 Modulates Telomerase Activity

Abstract

Apoptosis is a physiological mechanism of cell death that plays an important role in the regulation of tissue homeostasis. The regulation of apoptosis is a complex process and involves a number of gene products including the survival factor Bcl-2, which has been found to be frequently deregulated in human cancers. In addition to deregulation of apoptosis, the process of neoplasia is also believed to be driven by the activation of telomerase, a ribonucleoprotein complex that adds telomeric repeats (hexanucleotide 5 -TTAGGG-3 ) to the ends of replicating chromosomes. Activation of telomerase has been detected in a vast majority of human cancer cells. Although recent studies have demonstrated the wide occurrence of telomerase activation and Bcl-2 deregulation in human cancer cells, it remains unclear whether there is any linkage between the deregulation of Bcl-2 and telomerase activity in cancer cells. In the studies presented here, we report that the stable overexpression of Bcl-2 in human cancer cells with low Bcl-2 expression was accompanied by increased levels of telomerase activity. In addition, using an IL-2-dependent cytotoxic T-cell line, CTLL-2, we demonstrated that IL-2 deprivation (8 h), which is known to down-regulate Bcl-2 expression, also resulted in concurrent inhibition of telomerase activity in the absence of any detectable apoptosis and accumulation of cells in the G 0 /G 1 phase of the cell cycle. Re-exposure of IL-2-deprived CTLL-2 cells to the recombinant IL-2 led to the up-regulation of both Bcl-2 expression and telomerase activity. Taken together, these findings establish a close linkage between the modulation of telomerase activity by survival factor Bcl-2, and provide a model to study regulation of telomerase activity by an anti-apoptotic pathway that is widely deregulated in cancer cells.

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

“…This agrees with the observation that p75 NGFR -positive cells are a subset of the Ki-67 negative population in vivo. Our conclusion may be relevant to the recent report that very high expression of bcl-2 modulates telomerase expression (Mandel and Kumar, 1997).…”

Telomerase activity and p53-dependent apoptosis in ovarian cancer cells

“…The appearance of p53-dependent apoptotic pathway may cause the higher sensitivity to CDDP in p53-transducted cells. Although it is reported that stable over-expression of Bcl-2 in cancer cells is accompanied by increased levels of telomerase activity (Mandal et al, 1997), Bcl-2 expression did not differ among all cell lines. CDDP causes DNA strand breaks especially at guanine residues followed by apoptosis (Pil et al, 1997).…”

Role of Ceramide in Mediating the Inhibition of Telomerase Activity in A549 Human Lung Adenocarcinoma Cells

“…There are data showing that the overexpression of Bcl-2 is associated with increased telomerase activity in some human cancer cells (40,41), but its overexpression had no effect on telomerase activity in human Jurkat T cells (42), suggesting that the effect of Bcl-2 on telomerase might be cell line-or tissue-specific. Our results, however, showed that overexpression of Bcl-2 did not have any significant effect on telomerase activity in A549 cells (data not shown).…”