Inhibition of telomerase by mutant template telomerase RNA and anti-telomerase short interfering RNA induces ALT in immortalized human esophageal epithelial cells

Introduction: Immortalization is an important step in the malignant transformation of human cells and essentially depends on telomere maintenance. This is either mediated through activation of the enzyme telomerase, which contains a template RNA moiety (hTER) and the core protein (hTERT) or through a recombination based alternative mechanism (ALT). Little is known about the regulation and coexistence of these two mechanisms in a single cell. Previously, we could demonstrate that the induction of the respective telomere maintenance mechanism is dependent on cell-cycle kinetics. Now we investigated, whether immort…