Telomeric DNA Induces Apoptosis and Senescence of Human Breast Carcinoma Cells

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dc.contributor.author Yaar, Mina en_US
dc.contributor.author Eller, Mark S en_US
dc.contributor.author Panova, Izabela en_US
dc.contributor.author Kubera, John en_US
dc.contributor.author Wee, Lee Hng en_US
dc.contributor.author Cowan, Kenneth H en_US
dc.contributor.author Gilchrest, Barbara A en_US
dc.date.accessioned 2012-01-11T22:29:18Z
dc.date.available 2012-01-11T22:29:18Z
dc.date.copyright 2007 en_US
dc.date.issued 2007-1-26 en_US
dc.identifier.citation Yaar, Mina, Mark S Eller, Izabela Panova, John Kubera, Lee Hng Wee, Kenneth H Cowan, Barbara A Gilchrest. "Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells" Breast Cancer Research 9(1):R13. (2007) en_US
dc.identifier.issn 1465-542X en_US
dc.identifier.uri http://hdl.handle.net/2144/3305
dc.description.abstract INTRODUCTION. Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. METHODS. The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. RESULTS. Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. CONCLUSION. By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies. en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2007 Yaar et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Telomeric DNA Induces Apoptosis and Senescence of Human Breast Carcinoma Cells en_US
dc.type article en_US
dc.identifier.doi 10.1186/bcr1646 en_US
dc.identifier.pubmedid 17257427 en_US
dc.identifier.pmcid 1851376 en_US

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