2005 Volume 15 Issue 2 Pages 15-26
Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in immortalized cells and most of human cancers but is quiescent in most normal somatic cells. Using a binary adenovirus system that can induce Bax gene expression, we showed that induction of Bax gene expression via the hTERT promoter elicited tumor-specific apoptosis in vitro, suppressed tumor growth in nude mice, and prevent the toxicity of Bax gene in vitro and in vitro. We constructed a tumor-specific replication-competent adenovirus, in which the hTERT promoter element drives expression of E1A and E1B genes. TRAD induced selective E1A and E1B expression in human cancer cells, but not in normal cells. TRAD replicated efficiently and induced marked cell killing in cancer cell lines,whereas replication as well as cytotoxicity was highly attenuated in normal human fibroblasts. In nu/nu mice carrying s.c. human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, non-injected tumors was demonstrated.
