Ding Jin, Zhang Ronghe, Li Jingxia, Xue Caifang, Huang Chuanshu
Department of Etiology, Fourth Military Medical University, 17 Chunglexi Road, Xi'an, Shaanxi, 770032, China.
Mol Cell Biochem. 2006 Jul;287(1-2):117-25. doi: 10.1007/s11010-005-9087-1. Epub 2006 Apr 28.
The results from animal studies have shown that mouse skin is highly susceptible to both ionizing radiation and benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE). Previous studies have also indicated that cyclin D1 plays a crucial role in controlling cell proliferation and tumorigenesis. We, therefore, investigated here the effect of ionizing radiation and B[a]PDE on cyclin D1 transcription and potential involvement of NFAT3 in regulation of cyclin D1 transcription in mouse epidermal Cl 41 cells. We found that B[a]PDE exposure induced a high level of NFAT activation and cyclin D1 transcription in mouse epidermal Cl 41 cells. Ionizing radiation exhibited an enhancement for NFAT activation and cyclin D1 induction by B[a]PDE, even though ionizing radiation by itself had only a marginal effect. By stably knockdown of NFAT3 protein expression using specific NFAT3 small interfering RNA (siRNA), we found that cyclin D1 induction by B[a]PDE or B[a]PDE plus ionizing radiation was dramatically impaired. These results indicate that ionizing radiation is able to enhance cyclin D1 transcription induced by B[a]PDE, and NFAT3 is involved in the regulation of cyclin D1 transcription by B[a]PDE or B[a]PDE plus ionizing radiation.
动物研究结果表明，小鼠皮肤对电离辐射和苯并[a]芘 - 7,8 - 二醇 - 9,10 - 环氧化物（B[a]PDE）高度敏感。先前的研究还表明，细胞周期蛋白D1在控制细胞增殖和肿瘤发生中起关键作用。因此，我们在此研究了电离辐射和B[a]PDE对细胞周期蛋白D1转录的影响，以及NFAT3在小鼠表皮Cl 41细胞中细胞周期蛋白D1转录调控中的潜在作用。我们发现，暴露于B[a]PDE可诱导小鼠表皮Cl 41细胞中高水平的NFAT激活和细胞周期蛋白D1转录。电离辐射增强了B[a]PDE诱导的NFAT激活和细胞周期蛋白D1表达，尽管电离辐射本身的影响很小。通过使用特异性NFAT3小干扰RNA（siRNA）稳定敲低NFAT3蛋白表达，我们发现B[a]PDE或B[a]PDE加电离辐射诱导的细胞周期蛋白D1表达显著受损。这些结果表明，电离辐射能够增强B[a]PDE诱导的细胞周期蛋白D1转录，并且NFAT3参与B[a]PDE或B[a]PDE加电离辐射对细胞周期蛋白D1转录的调控。
