Telomerase activity is down regulated via decreases in hTERT mRNA but not TEP1 mRNA or hTERC during the differentiation of leukemic cells

Background: Recent studies have determined several telomerase-associated mo lecules, but the precise mechanisms regulating telomerase activity by chose molecules has not been fully understood Materials and Methods: The telomer ase activity was determined by TRAP assay. Using TaqMan RT-PCR, the quantit ative and kinetic values of mRNA expression of the three telomerase-associa ted molecules were examined in HL60 cells differentiated with tumor necrosi s factor mutant and all-trans-retinoic acid Results: The levels of telomera se activity in leukemic cell lines, leukemic cells from patients, and norma l peripheral blood cells were distributed over a very wide range. Human tel omerase catalytic subunit (hTERT) mRNA expression declined to nearly undete ctable levels more rapidly than the inhibition of telomerase activity after treatment with these reagents in HL60 cells. Telomerase-associated protein (TEP1) mRNA inn eased approximately 6-fold over its level in untreated cel ls. The levels of human telomerase RNA component (hTERC) also increased app roximately 2.7-fold at 5 days after treatment. Conclusions: These results s uggest that telomerase activity is down-regulated mainly via decreases in h TERT, bur not TEP1 and hTERC expression during the differentiation of leuke mic cells.