Telomerase-a complex ribonucleoprotein enzyme-synthesizes telomeric repeats to avoid telomere loss that accompanies cell division and chromosomal replication. Expression of telomerase is detectable in embryonic cells and cancer cells, but not in normal human cells. On the other hand, in mice, substantial expression of telomerase is detected in normal cells and tissues as well as in immortalized cells. These results suggest that the regulatory mechanisms of telomerase activity in humans and mice differ. Considering these results along with the fact that the expression of the telomerase reverse transcriptase (TERT) gene is a rate-limiting step for telomerase activity, we compared transcriptional regulatory mechanisms of both the species. A series of luciferase assays and RT-PCR analyses demonstrated that c-Myc, a dominant transactivator for human TERT (hTERT), is not involved in the regulation of mouse TERT (mTERT). These results suggest that distinct molecules and pathways are involved in the process of immortalization and tumorigenesis in human and mouse cells.