Abstract：
:X-ray-induced damage leads to cell-cycle "checkpoint" arrest by p53-dependent induction of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1). Human tumor cells that lack this response fail to arrest after exposure to DNA-damaging agents, undergo multiple rounds of endoreduplicative DNA synthesis, and eventually commit to an apoptotic cell death. Since low oxygen tension can also induce p53 protein accumulation, and can lead to cell-cycle arrest or apoptosis, we examined the expression of p21 in tumor cells under normoxic and hypoxic conditions. In a survey of cells, mRNA for the p21 gene was induced two- to threefold in response to hypoxia in a seemingly p53-independent manner. We therefore examined genetically matched cells that differ in their p21 and p53 status for response to ionizing radiation and hypoxia. We found that both p21-deficient and p53-deficient cells exhibit an increase in chromosome instability, an increased level of apoptosis, and a failure to arrest after exposure to ionizing radiation. However, cells that lack either p21 or p53 exhibit no increase in chromosome instability or elevated apoptosis and still arrest in response to hypoxia. Thus, the mechanism responsible for the differential response to either hypoxia or X rays presumably lies in the control of cell-cycle progression in response to stress and its dependence on p21. Since the loss of a DNA-damage-dependent checkpoint does not sensitize cells to killing by stresses that elicit a DNA-damage-independent checkpoint, targeting the function of p21 pharmacologically will not kill tumor cells in situ in the absence of a DNA damage signal.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Denko NC,Green SL,Edwards D,Giaccia AJdoi
10.1006/excr.2000.4928keywords:
subject
Has Abstractpub_date
2000-07-10 00:00:00pages
82-91issue
1eissn
0014-4827issn
1090-2422pii
S0014-4827(00)94928-0journal_volume
258pub_type
杂志文章abstract：:The rapidity of the optional 90-min differentiation of Naegleria gruberi from amoebae to flagellates suggests the possibility of a free-running cascade of events from initiating stimulus through gene expression to organelle assembly and cell morphogenesis. Instead our experiments reveal two points early in the differe...
journal_title：Experimental cell research
pub_type： 杂志文章
doi：10.1006/excr.1998.4121
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abstract：:Nitric oxide (NO) markedly induces cardiomyocyte (CM) differentiation of embryonic stem (ES) cells. Here we examined the role of the Ca(2+) signaling in the NO-induced CM differentiation of mouse ES cells. We found that NO induced intracellular Ca(2+) increases in ES cells in a dose-dependent manner, and application o...
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journal_title：Experimental cell research
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abstract：:Secretory phospholipase A(2) (sPLA(2)) plays important roles in mediating various cellular processes, including cell proliferation, differentiation, apoptosis, and inflammatory response. In this study, we demonstrated that a basic sPLA(2) inhibits epidermal growth factor (EGF)-induced EGF receptor activation, as deter...
journal_title：Experimental cell research
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journal_title：Experimental cell research
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journal_title：Experimental cell research
pub_type： 杂志文章
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journal_title：Experimental cell research
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journal_title：Experimental cell research
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journal_title：Experimental cell research
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journal_title：Experimental cell research
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journal_title：Experimental cell research
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journal_title：Experimental cell research
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pub_type： 杂志文章
doi：10.1006/excr.1998.4027
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