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Journal of Biomedicine and Biotechnology
Volume 2004 (2004), Issue 4, Pages 185-194
http://dx.doi.org/10.1155/S1110724304403131
Research article

Retrotransposition-Competent Human LINE-1 Induces Apoptosis in Cancer Cells With Intact p53

1Department of Microbiology and Molecular Cell Biology and Virginia Prostate Center, Eastern Virginia Medical School, Lewis Hall #3011, 700 West Olney Road, Norfolk, VA 23501, USA
2Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709-2233, USA
3Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709-2233, USA

Received 16 March 2004; Revised 17 April 2004; Accepted 29 April 2004

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Retrotransposition of human LINE-1 (L1) element, a major representative non-LTR retrotransposon in the human genome, is known to be a source of insertional mutagenesis. However, nothing is known about effects of L1 retrotransposition on cell growth and differentiation. To investigate the potential for such biological effects and the impact that human L1 retrotransposition has upon cancer cell growth, we examined a panel of human L1 transformed cell lines following a complete retrotransposition process. The results demonstrated that transposition of L1 leads to the activation of the p53-mediated apoptotic pathway in human cancer cells that possess a wild-type p53. In addition, we found that inactivation of p53 in cells, where L1 was undergoing retrotransposition, inhibited the induction of apoptosis. This suggests an association between active retrotransposition and a competent p53 response in which induction of apoptosis is a major outcome. These data are consistent with a model in which human retrotransposition is sensed by the cell as a “genetic damaging event” and that massive retrotransposition triggers signaling pathways resulting in apoptosis.