title: TRF2 inhibition promotes anchorage-independent growth of telomerase-positive human fibroblasts.
abstract: Although telomere instability is observed in human tumors and is associated with the development of cancers in mice, it has yet to be established that it can contribute to the malignant transformation of human cells. We show here that in checkpoint-compromised telomerase-positive human fibroblasts an episode of TRF2 inhibition promotes heritable changes that increase the ability to grow in soft agar, but not tumor growth in nude mice. This transforming activity is associated to a burst of telomere instability but is independent of an altered control of telomere length. Moreover, it cannot be recapitulated by an increase in chromosome breaks induced by an exposure to gamma-radiations. Since it can be revealed in the context of telomerase-proficient human cells, telomere dysfunction might contribute to cancer progression even at late stages of the oncogenesis process, after the telomerase reactivation step.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Cellule of Ecole Normale Supérieure de Lyon, UMR CNRS/INRA/ENS, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Brunori
authors.forename: N
authors.initials: N
authors.lastname: Mathieu
authors.forename: M
authors.initials: M
authors.lastname: Ricoul
authors.forename: S
authors.initials: S
authors.lastname: Bauwens
authors.forename: C E
authors.initials: CE
authors.lastname: Koering
authors.forename: A
authors.initials: A
authors.lastname: Roborel de Climens
authors.forename: A
authors.initials: A
authors.lastname: Belleville
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: Puisieux
authors.forename: D
authors.initials: D
authors.lastname: Décimo
authors.forename: A
authors.initials: A
authors.lastname: Puisieux
authors.forename: L
authors.initials: L
authors.lastname: Sabatier
authors.forename: E
authors.initials: E
authors.lastname: Gilson
mesh_terms: D000483:Alleles; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D013539:Simian virus 40 / Q000235:genetics; D019098:Telomerase / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase