Telomerase is almost universally required for cellular immortality and is permissive for tumorigenesis. Accumulating evidence suggests that telomerase may have roles in cellular processes independent of its role in telomere maintenance. However, the biochemical properties and the mechanisms of telomerase non-telomeric functions are unknown. In this report, we show that the telomerase catalytic component hTERT is capable of activating transcription of VEGF. We further demonstrated that the activation of VEGF expression by hTERT was independent of telomerase activity and telomere maintenance. These results suggest that hTERT has non-telomeric activity in the regulation of gene expression and provide additional insights into the role of telomerase in aging and cancer. (C) 2009 Elsevier Inc. All rights reserved.