Use of transcriptional regulatory sequences of telomerase (hTER and hTERT)for selective killing of cancer cells

Telomerase (hTER and hTERT) plays a crucial role in cellular immortalizatio n and carcinogenesis. Telomerase activity can be detected in about 85% of d ifferent malignant tumors, but is absent in most normal cells. In situ hybr idization analysis showed that high levels of hTER and hTERT expression are present in bladder cancer, while no signal was detected in normal tissue. Therefore, in this work we propose to use hTER and hTERT transcriptional re gulatory sequences to control the expression of a cytotoxic gene in bladder tumor cells, resulting in the selective destruction of this cell populatio n. Expression vectors containing the diphtheria toxin A-chain (DT-A) gene w ere linked to hTER and hTERT transcriptional regulatory sequences, respecti vely. Inhibition of protein synthesis occurred in bladder and hepatocellula r carcinoma cells transfected with the plasmids containing the DT-A gene un der the control of the hTER or hTERT promoters in correlation with their ac tivity. These studies support the feasibility of using hTER and hTERT trans criptional regulatory sequences for targeted patient-oriented gene therapy of human cancer.