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KMID : 0385220030130010001
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Korean Journal of Gerontology
2003 Volume.13 No. 1 p.1 ~ p.7
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Senescence as a Cell Cycle Exit and Tumor Suppression Mechanisms
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Abstract
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The proliferative lifespan of normal mammalian cells is limited by replicative senescence (Campisi, 1997; Hayflick, 1961), a process that appears to be primarily mediated by gradual shortening of telomeres (Shay, 1997). Senescent cells withdraw irreversibly from the cell cycle, but remain viable indefinitely, and display characteristic phenotypic markers, such as enlarged and flattened morphology, irreversible growth arrest, and expression of the senescence-associated-b-galactosidase (SA-b-Gal) activity at pH 6.0 (Dimri et al., 1995). Recently, it has been shown that expression of ras and raf oncogenes can induce a rapid onset of replicative senescence in normal fibroblast cells associated with induction of p53, p21, p16, and hypophosphorylation of Rb protein (Serrano et al., 1997; Zhu et al., 1998), implicating that replicative senescence, like apoptosis, is a programmed response of the organism to potentially oncogenic impact. Tumor cells are capable of extended proliferation as if the capability to become senescent has been somehow repressed or lost. Recently we and other groups have reported that certain tumor cells enter into senescence state by expression of tumor suppressor genes such as p53 (Jung et al., 2001; Shin et al., 1997), Rb (Xu et al., 1997), p21 (Fang et al., 1999), and p16 (Uhrbom et al., 1997). Although these studies suggest that tumor suppressor genes are essential for oncogene-induced senescence in normal HDF and their expression can induce senescence in human tumor cells, detailed mechanisms of senescence induction have not been understood. There is therefore a great deal of interest in identifying genes that are involved in tumor suppressor gene-induced senescence.
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KEYWORD
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senescence, p53, p38, cell cycle, p21
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