Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:879-889 (2006)
© 2006 The Gerontological Society of America

Expression Profiling Identifies Three Pathways Altered in Cellular Immortalization: Interferon, Cell Cycle, and Cytoskeleton

Aviva Levine Fridman, Lin Tang, Olga I. Kulaeva, Bin Ye, Qunfang Li, Fatimah Nahhas, Paul C. Roberts, Susan J. Land, Judith Abrams and Michael A. Tainsky1,

1 Program in Molecular Biology and Human Genetics, Barbara Ann Karmanos Cancer Institute, and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan.
2 Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan.
3 Biostatistics Core, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.

Address correspondence to Michael A. Tainsky, PhD, Program in Molecular Biology and Human Genetics, Barbara Ann Karmanos Cancer Institute, and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 110 East Warren Ave., Detroit, Michigan, 48201. E-mail: tainskym{at}karmanos.org

Abrogation of cellular senescence, resulting in immortalization, is a necessary step in the tumorigenic transformation of a cell. Four independent, spontaneously immortalized Li-Fraumeni syndrome (LFS) cell lines were used to analyze the gene expression changes that may have given these cell lines the growth advantage required to become immortal. A cellular senescence–like phenotype can be induced in immortal LFS cells by treating them with the DNA methyltransferase (DNMT) inhibitor 5-aza-deoxycytidine. We hypothesized, therefore, that genes epigenetically silenced by promoter methylation are potentially key regulators of senescence. We used microarrays to compare the epigenetic gene expression profiles of precrisis LFS cells with immortal LFS cells. Gene ontology analysis of the expression data revealed a statistically significant contribution of interferon pathway, cell cycle, and cytoskeletal genes in the process of immortalization. The identification of the genes and pathways regulating immortalization will lead to a better understanding of cellular immortalization and molecular targets in cancer and aging.







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