Telomerase activity in cancer as a diagnostic and therapeutic target

Abstract

Major advances have been made in understanding the role of telomerase in cellular immortalization and carcinogenesis. Human telomeres undergo progressive shortening with cell division, and critical shortening of telomeres with cellular aging triggers a signal for cells to stop dividing and senesce. Telomerase is an enzyme that adds telomeric-repeated sequences to the ends of human chromosome DNA. Telomerase is active in the vast majority of tumors, but not in normal somatic tissues, and prevents progressive shortening of telomeres with cell division, probably giving tumor cells a growth advantage over normal cells. Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay provided the means to analyze telomerase in a wide variety of tissues. Evidence has been accumulated that this assay may be useful as a potential diagnostic tool for cancer. The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers. The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles. Understanding of such mechanisms might provide insight into molecular basis of human carcinogenesis and contributes to the development of novel cancer gene therapy targeting telomerase.