Telomerase, Telomerase Inhibition, and Cancer

Abstract

Telomeres, located at the ends of eukaryotic chromosomes, are synthesized by the enzyme telomerase and are responsible for maintaining chromosome length. The absence of telomerase in most somatic cells has been associated with telomere shortening and aging of these cells. In contrast, high levels of telomerase activity are observed in over 90% of human cancer cells. The absence of telomerase in normal and aging cells is considered a natural defense against development of cancer. However, we do not know what triggers the reappearance of telomerase in cancer cells. Telomerase activity is directly correlated with the expression of its active catalytic component, the human telomerase reverse transcriptase (hTERT), which is believed to be controlled primarily at the level of transcription. Elucidation of the control of telomerase in aging and in cancer as an age-related disease has considerable potential in leading to novel approaches in anti-aging medicine.

Kinetics of the DNA polymerase pyrococcus kodakaraensis

“…Specifi c template-directed nucleic acid synthesis is one of the greatest biochemical discoveries (Grundberg-Manago et al, 1955 andLehman, 2003). The accuracy, relative ability to bypass lesions and ability to elongate polymers processively makes these enzymes crucial to understanding such biological processes as infection, cancer and aging and also identifi es them as important drug targets (Ahmed andTollefsbol, 2003 andMiura andIzuta, 2004). Finally, template-directed nucleic acid polymerases are used in many procedures basic to modern biotechnology including PCR-based recombinant DNA technology, diagnostics and DNA sequencing (Smith, 1980 andSaiki et al, 1985).…”

Molecular Biomarkers Correlate with Disease-Free Survival in Patients with Anal Canal Carcinoma Treated with Chemoradiation

“…Increased expression of hTERT enhances cell survival and confers genome stability after exposure to ionizing radiation [47]. Highest hTERT expression correlated with therapeutic failure and worse prognosis [48]. The epidermal growth factor receptor (EGFR) signaling pathway is often overexpressed in many cancers and may be responsible for malignant transformation and progression [49,50].…”

Normal and Tumour Tissue mRNA Expressions of Telomerase Complex Genes in Several Types of Cancer

“…Most malignant cancers (85-90%) are known to show high telomerase activity for cellular immortality (12). Although the absence of telomerase in normal cells is considered a natural defence against the development of cancer, telomerase is thought to reappear in cancer cells through multiple mechanisms (13). hTERT is the rate-limiting determinant in telomerase activation (14).…”