| Expression profiling identifies three pathways altered in cellular immortalization: interferon, cell cycle, and cytoskeleton. | |
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MedLine Citation:
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PMID: 16960018 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Aviva Levine Fridman; Lin Tang; Olga I Kulaeva; Bin Ye; Qunfang Li; Fatimah Nahhas; Paul C Roberts; Susan J Land; Judith Abrams; Michael A Tainsky |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journals of gerontology. Series A, Biological sciences and medical sciences Volume: 61 ISSN: 1079-5006 ISO Abbreviation: J. Gerontol. A Biol. Sci. Med. Sci. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-08 Completed Date: 2006-10-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9502837 Medline TA: J Gerontol A Biol Sci Med Sci Country: United States |
Other Details:
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Languages: eng Pagination: 879-89 Citation Subset: AIM; IM |
Affiliation:
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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, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Azacitidine
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analogs & derivatives,
pharmacology Cell Aging Cell Cycle Cell Line, Tumor Cytoskeleton / genetics DNA Methylation Down-Regulation Enzyme Inhibitors / pharmacology Epigenesis, Genetic* Female Fibroblasts / metabolism Gene Expression Profiling* Genes, p53 Humans Interferon Regulatory Factor-7 / metabolism Interferon-alpha / metabolism Interferon-beta / metabolism Li-Fraumeni Syndrome / genetics*, metabolism Male Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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P30CA022453/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Interferon Regulatory Factor-7; 0/Interferon-alpha; 2353-33-5/decitabine; 320-67-2/Azacitidine; 77238-31-4/Interferon-beta |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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