This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gosink, E. C. Articles by McKinnon, P. J. Search for Related Content PubMed PubMed Citation Articles by Gosink, E. C. Articles by McKinnon, P. J.

Ataxia Telangiectasia Mutated Deficiency Affects Astrocyte Growth but not Radiosensitivity¹

Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105

The cancer-prone neurodegenerative disorder, ataxia telangiectasia (A-T), results from mutations of ATM (ataxia telangiectasia mutated). Individuals with A-T are also hypersensitive to ionizing radiation (IR). Cultured cells from A-T individuals or Atm-/- mice have cell cycle and growth defects and are generally considered radiosensitive. However, it has been shown recently that cell populations in the Atm-/- central nervous system are radioresistant. To define specific IR sensitivities of neural populations, we analyzed Atm-/- astrocytes. Here we show that Atm-/- astrocytes exhibit premature senescence, express constitutively high levels of p21, and have impaired p53 stabilization. However, in contrast to radiosensitive Atm-/- fibroblasts and radioresistant Atm-/- neurons, survival of Atm-/- astrocytes after IR was similar to wild-type astrocytes. Additionally, p53-null astrocytes, but not fibroblasts, were moderately more radioresistant than their wild-type counterparts, suggesting that the deficit in p53 stabilization observed in Atm-null cells is not a measure of radiation susceptibility. Thus, in astrocytes, the function of Atm in cellular growth and radiosensitivity is distinct. These data may have implications for ATM disruption strategies as a radiosensitizing treatment for brain tumors.

This article has been cited by other articles:

				I. Hickson, Y. Zhao, C. J. Richardson, S. J. Green, N. M. B. Martin, A. I. Orr, P. M. Reaper, S. P. Jackson, N. J. Curtin, and G. C. M. Smith Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM Cancer Res., December 15, 2004; 64(24): 9152 - 9159. [Abstract] [Full Text] [PDF]

				X. Zhu, C.-H. Kwon, P. W. Schlosshauer, L. H. Ellenson, and S. J. Baker PTEN Induces G1 Cell Cycle Arrest and Decreases Cyclin D3 Levels in Endometrial Carcinoma Cells Cancer Res., June 1, 2001; 61(11): 4569 - 4575. [Abstract] [Full Text] [PDF]