Pastila Riikka, Leszczynski Dariusz
Non-ionizing Radiation Laboratory, STUK-Radiation and Nuclear Safety Authority, Helsinki, Finland.
Cancer Cell Int. 2007 May 2;7:7. doi: 10.1186/1475-2867-7-7.
We have previously shown that ultraviolet-A (UVA) radiation enhances metastatic lung colonization capacity of B16-F1 melanoma cells. The aim of this study was to examine changes in expression profile of genes in mouse melanoma B16-F1 cells exposed to UVA radiation.
B16-F1 melanoma cells were exposed to a single UVA radiation dose of 8 J/cm2 and mRNA was isolated 4 h after the end of UVA exposure. Atlas Mouse Cancer 1.2 cDNA expression arrays were used for the large-scale screening to identify the genes involved in the regulation of carcinogenesis, tumor progression and metastasis. Physiologically relevant UVA dose induced differential expression in 9 genes in the UVA exposed melanoma cells as compared to the unexposed control cells. The expression of seven genes out of nine was upregulated (HSC70, HSP86, alpha-B-crystallin, GST mu2, Oxidative stress induced protein OSI, VEGF, cyclin G), whereas the expression of two genes was down-regulated (G-actin, non-muscle cofilin). The gene expression of cyclin G was mostly affected by UVA radiation, increasing by 4.85-folds 4 hour after exposure. The analysis of cyclin G protein expression revealed 1.36-fold increase at the 6 hour time point after UVA exposure. Cell cycle arrest in G2/M phase, which is known to be regulated by cyclin G, occurred at 4-h hour time-point, peaking 8 hours after the end of UVA irradiation, suggesting that cyclin G might play a role in the cell cycle arrest.
Our results suggest that UVA radiation-induces changes in the expression of several genes. Some of these changes, e.g. in expression of cyclin G, possibly might affect cell physiology (cell cycle arrest).
我们之前已经表明,紫外线A(UVA)辐射可增强B16-F1黑色素瘤细胞的肺转移定植能力。本研究的目的是检测暴露于UVA辐射的小鼠黑色素瘤B16-F1细胞中基因表达谱的变化。
将B16-F1黑色素瘤细胞暴露于8 J/cm2的单次UVA辐射剂量下,在UVA暴露结束后4小时分离mRNA。使用Atlas Mouse Cancer 1.2 cDNA表达阵列进行大规模筛选,以鉴定参与致癌作用、肿瘤进展和转移调节的基因。与未暴露的对照细胞相比,生理相关的UVA剂量诱导了UVA暴露的黑色素瘤细胞中9个基因的差异表达。9个基因中有7个基因的表达上调(热休克蛋白70、热休克蛋白86、α-B-晶状体蛋白、谷胱甘肽S-转移酶μ2、氧化应激诱导蛋白OSI、血管内皮生长因子、细胞周期蛋白G),而2个基因的表达下调(G-肌动蛋白、非肌肉丝切蛋白)。细胞周期蛋白G的基因表达受UVA辐射影响最大,暴露后4小时增加4.85倍。细胞周期蛋白G蛋白表达分析显示,UVA暴露后6小时时间点增加1.36倍。已知由细胞周期蛋白G调节的G2/M期细胞周期阻滞发生在4小时时间点,在UVA照射结束后8小时达到峰值,表明细胞周期蛋白G可能在细胞周期阻滞中起作用。
我们的结果表明,UVA辐射诱导了几个基因表达的变化。其中一些变化,例如细胞周期蛋白G的表达变化,可能会影响细胞生理学(细胞周期阻滞)。