title: Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition.
abstract: The majority of human malignancies use telomerase to maintain telomere homeostasis. Antitelomerase therapy is therefore a promising approach for a cancer-specific therapy. The alternative lengthening of telomeres pathway (ALT) is a recombination-based, telomerase-independent mechanism of telomere length control. It is widely believed that ALT could be engaged when cancer cells escape from telomerase inhibition. However, no reports exist that would support this concept of therapy resistance. We inhibited telomerase in a human cancer cell line with a mismatch repair defect and observed a telomerase-independent, ALT-like telomere elongation. This is the first report of inducing a telomerase-independent telomere elongation in human cancer cells when telomerase is inhibited, thus describing a novel mechanism of resistance to antitelomerase therapy.
authors.affiliation: University of Innsbruck, Department of Internal Medicine, Innsbruck, Austria.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Bechter
authors.forename: Ying
authors.initials: Y
authors.lastname: Zou
authors.forename: William
authors.initials: W
authors.lastname: Walker
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008819:Mice, Nude; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C102997:Msh6 protein, mouse; D019098:Telomerase