Identification of skin injury-related genes induced by ionizing radiation in human keratinocytes using cDNA microarray

被引:26
作者
Koike, M [1 ]
Shiomi, T [1 ]
Koike, A [1 ]
机构
[1] Natl Inst Radiol Sci, Radiat Hazards Res Grp, Inage Ku, Chiba 2638555, Japan
关键词
D O I
10.1269/jrr.46.173
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The skin is an external organ that is most frequently exposed to radiation. High-dose radiation initiates and promotes skin cancer and acute radiation injury. It is important to investigate the influence of high-dose radiation exposure on the skin at the molecular level to understand acute radiation injury. To identify genes that are associated with injury caused by high-dose radiation exposure of the skin, we used microarray technology to examine the effect of irradiation on approximately 1000 genes in normal human epidermal keratinocytes at 3 It postirradiation with a cytotoxic dose of X-ray (5 Gy). We found that 16 and 59 genes were up- and down-regulated respectively in the keratinocytes. Several apoptosis-related genes, for example, BAK and TSC-22, and anti-proliferative genes, for example, BTG-1 and BTG-3, were up-regulated. We focused on ATF3 because ATF3 is induced most strongly by X-irradiation, and its function in keratinocytes is unknown. The induction of the ATF3 mRNA and protein in keratinocytes following Xray was confirmed by RT-PCR and western blot analysis. ATF3 was also induced and accumulated within the nuclei of keratinocytes after X-ray irradiation in vivo and in vitro. Exogenous EYFP-ATF3 also accumulated within the nuclei of keratinocytes. lit the transient expression assay, EYFP-ATF3, but not EYFP, induced apoptosis in keratinocytes. Taken together, these results Suggest that ATF3. plays a role in apoptosis in keratinocytes and is associated with skin injury caused by ionizing radiation.
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页码:173 / 184
页数:12
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