title: Characterization of ataxia telangiectasia fibroblasts with extended life-span through telomerase expression.
abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by progressive cerebellar degeneration, immunodeficiencies, genomic instability and gonadal atrophy. A-T patients are hypersensitive to ionizing radiation and have an elevated cancer risk. Cells derived from A-T patients require higher levels of serum factors, exhibit cytoskeletal defects and undergo premature senescence in culture. We show here that expression of the catalytic subunit of telomerase (hTERT) in primary A-T patient fibroblasts can rescue the premature senescence phenotype. Ectopic expression of hTERT does not rescue the radiosensitivity or the telomere fusions in A-T fibroblasts. The hTERT+AT cells also retain the characteristic defects in cell-cycle checkpoints, and show increased chromosome damage before and after ionizing radiation. Although A-T patients have an increased susceptibility to cancer, the expression of hTERT in A-T fibroblasts does not stimulate malignant transformation. These immortalized A-T cells provide a more stable cell system to investigate the molecular mechanisms underlying the cellular phenotypes of Ataxia-telangiectasia.
authors: Department of Biology, University of California San Diego, La Jolla, California, CA 92093-0322, USA.
authors: L D
authors: LD
authors: Wood
authors: T L
authors: TL
authors: Halvorsen
authors: S
authors: S
authors: Dhar
authors: J A
authors: JA
authors: Baur
authors: R K
authors: RK
authors: Pandita
authors: W E
authors: WE
authors: Wright
authors: M P
authors: MP
authors: Hande
authors: G
authors: G
authors: Calaf
authors: T K
authors: TK
authors: Hei
authors: F
authors: F
authors: Levine
authors: J W
authors: JW
authors: Shay
authors: J J
authors: JJ
authors: Wang
authors: T K
authors: TK
authors: Pandita
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015197:Carcinogenicity Tests; D002453:Cell Cycle / Q000528:radiation effects; D002461:Cell Line, Transformed; D016922:Cellular Senescence; D002877:Chromosomes, Human / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects* / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012313:RNA; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D012016:Reference Values; D012190:Retroviridae / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase