Telomerase plays a key role in the maintenance of
chromosomal stability in
tumors, but the mechanism regulating
telomerase activity is still unclear. Recent studies have suggested that c-myc may be vital for regulation of hTERT
mRNA expression and
telomerase activity. In this study, we investigated the changes of
telomerase activity and
telomerase-related genes induced by
herbimycin A in K562 human chronic myelogeous leukemic cells.
Telomerase activity showed a biphasic pattern in
herbimycin A-treated K562 cells. Initially, the
telomerase activity decreased along with the decline of cells in S and G2/M phases, but it recovered slightly at the end of treatment. Expression of
mRNA for the
telomerase catalytic subunit (hTERT) was decreased before the decline of
telomerase activity, and increased slightly before the reactivation of
telomerase activity. During
herbimycin A treatment, both c-myc and
cyclin D1 mRNA showed transient downregulation before the increase of G1 cells.
Herbimycin A treatment caused the downregulation of both
telomerase activity and hTERT
mRNA in
cyclin D1-transfected K562 cells, while
telomerase activity was partially restored in c-Myc-transfected cells. In contrast, hTERT-transfected K562 cells maintained a high level of
telomerase activity during
herbimycin A treatment. Neither the template
RNA component of
telomerase (
hTERC) nor
telomerase-associated
protein (TEP-1) were altered in any of the transfected K562 cells. These results indicate that
telomerase activity is mainly regulated by hTERT, and that c-Myc
protein is one of the positive regulators of hTERT in leukemic cells but is not enough to counteract the downregulation of
telomerase activity by
herbimycin A completely.