Chen Rui, Li Aiping, Zhu Ting, Li Chunping, Liu Qizhan, Chang Hebron C, Zhou Jianwei
Department of Molecular Cell Biology and Toxicology, Jiangsu Provincial Key Laboratories of Human Functional Genomics and Applied Toxicology, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
J Toxicol Environ Health A. 2005 Mar 26;68(6):445-56. doi: 10.1080/15287390590903711.
The pyrethroid insecticide fenvalerate and the organophosphorus insecticide phoxim are now the most widely used agents for indoor pest control in China. Fenvalerate was shown to mimic estrogenic activity, whereas phoxim did not induce similar effects. Our previous studies demonstrated that JWA, a novel retinoic acid-inducible and cytoskeleton-associated gene, is also a potential environmental-responsive gene with increased expression to oxidative and heat-shock stresses. In the present study, the influence of both fenvalerate and phoxim was examined on the expression of JWA in MCF-7 (ER+) and MDA-MB-231 (ER-) human breast carcinoma cell lines. Concentrations of 0.01, 1, and 100 micromol/L of fenvalerate or phoxim were selected to treat both MCF-7 and MDA-MB-231 cells at 1, 3, and 5 d, respectively. The MTT results only showed that fenvalerate stimulated MCF-7 cell proliferation. Western blot assay was employed to detect the expressions of JWA and heat-shock proteins (hsp27 and hsp70). The results showed that after treatment with fenvalerate, both JWA and hsp70 showed similar expression patterns in the both cell lines; however, all the expression patterns of JWA, hsp27, and hsp70 were evidently reversed between ER+ and ER- cells. In addition, phoxim-treated cells showed a concentration-dependent relationship in JWA expression at all time points. These results suggest that JWA has similar functions with respect to hsp27 and hsp70, and might be a novel signal molecule in estrogen receptor-related signal transduction pathways in mammalian cells.
拟除虫菊酯类杀虫剂氰戊菊酯和有机磷杀虫剂辛硫磷是目前中国室内害虫防治中使用最广泛的药剂。氰戊菊酯被证明具有模拟雌激素活性的作用，而辛硫磷未诱导出类似效应。我们之前的研究表明，JWA是一种新的视黄酸诱导且与细胞骨架相关的基因，也是一种潜在的环境响应基因，其表达在氧化应激和热休克应激下会增加。在本研究中，检测了氰戊菊酯和辛硫磷对MCF-7（雌激素受体阳性）和MDA-MB-231（雌激素受体阴性）人乳腺癌细胞系中JWA表达的影响。分别选择0.01、1和100 μmol/L的氰戊菊酯或辛硫磷浓度，在第1、3和5天分别处理MCF-7和MDA-MB-231细胞。MTT结果仅显示氰戊菊酯刺激MCF-7细胞增殖。采用蛋白质免疫印迹法检测JWA和热休克蛋白（hsp27和hsp70）的表达。结果显示，用氰戊菊酯处理后，JWA和hsp70在两种细胞系中表现出相似的表达模式；然而，JWA、hsp27和hsp70在雌激素受体阳性和阴性细胞之间的所有表达模式明显相反。此外，辛硫磷处理的细胞在所有时间点JWA表达均呈现浓度依赖性关系。这些结果表明，JWA在hsp27和hsp70方面具有相似功能，可能是哺乳动物细胞雌激素受体相关信号转导途径中的一种新的信号分子。
