Anti-apoptotic role of telomerase following gamma-irradiation in human leukemia cell lines of different p53 status

Full text: Telomerase is a ribonucleoprotein involved in telomere maintenance and in DNA repair and cell survival. Apoptosis is a key mechanism that controls cell viability. We investigated the relationship between telomerase activity (TA) and apoptosis in gamma-irradiated p53+ Molt4 and p53- KG1a cells. Radiation-induced TA up-regulation was maximal in both cell types 24 h-post-irradiation (p.i.), coinciding with an accumulation of hTERT mARN. PARP inhibition by 3-aminobenzamide and PI3K inhibition by wortmannin partially abrogated this up-regulation. Wortmannin abolished radiation-induced hTERT mRNA accumulation only in Molt4 cells. Radiation-induced apoptosis and G2/M arrest was evident from 4 h-p.i. in Molt4 cells, whereas the G2/M block in KG1a cells was observed at 24 h-p.i., after which apoptosis began to increase. Early radiation-induced apoptosis was enhanced by 3-AB and wortmannin in Molt4 cells. While 3-AB increased late apoptosis in KG1a cells, they were not radio sensitized by wortmannin. Radiation-induced G2/M blockage was abolished in both cell lines by 3-AB, but only by wortmannin in Molt4 cells. These findings suggest an anti-apoptotic role for telomerase that is closely related to p53 status. Telomerase was able to partially block radiation-induced early p53-dependent apoptosis in Molt4 cells, but did not seem to be involved in the modulation of late radiation-induced apoptosis in KG1a cells. (author)