Ventura C, Núñez M, Gaido V, Pontillo C, Miret N, Randi A, Cocca C
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Toxicol Lett. 2017 Mar 15;270:72-79. doi: 10.1016/j.toxlet.2017.02.013. Epub 2017 Feb 12.
Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7. Here, we show that HCB alters cell cycle in a concentration-dependent way. The lowest assessed concentration (0.005μM) promotes the cell cycle progression, enhances cyclin D expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5μM HCB delays the cell cycle progression and promotes the formation of the cyclin E-CDK2-p27 protein complex. Our results show that HCB stimulates cell proliferation through cell cycle modulation and c-Src involvement in MCF-7 cells. Here, we report for the first time that differential mechanisms of action of HCB on mammary cell cycle progression are triggered at different concentrations of this pollutant.
六氯苯（HCB）是一种有机氯污染物，广泛分布于全球环境中。我们团队和其他团队之前的报告表明，这种化合物是一种内分泌干扰物。我们还报告称，HCB在N-亚硝基-N-甲基脲诱导的大鼠乳腺肿瘤中具有协同致癌作用。在这项工作中，我们研究了HCB对雌激素敏感的乳腺癌细胞系MCF-7细胞周期进程和细胞周期调节蛋白表达的影响。在此，我们表明HCB以浓度依赖的方式改变细胞周期。评估的最低浓度（0.005μM）促进细胞周期进程，增强细胞周期蛋白D的表达，并减少p27的核定位，同时p27与c-Src激酶之间的相互作用增加。另一方面，5μM HCB延迟细胞周期进程并促进细胞周期蛋白E-CDK2-p27蛋白复合物的形成。我们的结果表明，HCB通过调节细胞周期和c-Src参与刺激MCF-7细胞的增殖。在此，我们首次报告，HCB对乳腺细胞周期进程的不同作用机制在该污染物的不同浓度下被触发。
