Department of Genetics and Molecular Biology, Center for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
Exp Cell Res. 2013 Oct 15;319(17):2588-603. doi: 10.1016/j.yexcr.2013.07.028. Epub 2013 Aug 12.
We have studied the expression of the tight junction proteins (TJ) occludin, claudin-1 and ZO-2 in the epidermis of female mice. We observed a peak of expression of these proteins at postnatal day 7 and a decrease in 6 week-old mice to values similar to those found in newborn animals. We explored if the expression of the E6 oncoprotein from high-risk human papilloma virus type 16 (HPV16) in the skin of transgenic female mice (K14E6), altered TJ protein expression in a manner sensitive to ovarian hormones. We observed that in ovariectomized mice E6 up-regulates the expression of occludin and ZO-2 in the epidermis and that this effect was canceled by 17β-estradiol. Progesterone instead induced occludin and ZO-2 over-expression. However, the decreased expression of occludin and ZO-2 induced by 17β-estradiol in the epidermis was not overturned by E6 or progesterone. In addition, we employed MDCK cells transfected with E6, and observed that ZO-2 delocalizes from TJs and accumulates in the cell nuclei due to a decrease in the turnover rate of the protein. These results reinforce the view of 17β-estradiol and E6 as risk factors for the development of cancer through effects on expression and mislocalization of TJ proteins.
我们研究了雌性小鼠表皮中紧密连接蛋白（TJ）occludin、claudin-1 和 ZO-2 的表达。我们观察到这些蛋白在出生后第 7 天表达达到峰值，而在 6 周龄小鼠中表达下降至与新生动物相似的水平。我们探讨了高危型人乳头瘤病毒 16 型（HPV16）E6 癌蛋白在转基因雌性小鼠（K14E6）皮肤中的表达是否以对卵巢激素敏感的方式改变 TJ 蛋白的表达。我们观察到，在卵巢切除的小鼠中，E6 上调了表皮中 occludin 和 ZO-2 的表达，而 17β-雌二醇可使这种作用逆转。相反，孕激素诱导 occludin 和 ZO-2 的过表达。然而，17β-雌二醇在表皮中诱导的 occludin 和 ZO-2 表达下调并未被 E6 或孕激素逆转。此外，我们还利用转染 E6 的 MDCK 细胞进行实验，观察到由于蛋白周转率降低，ZO-2 从 TJ 移位并在细胞核中积累。这些结果强化了 17β-雌二醇和 E6 通过对 TJ 蛋白表达和定位的影响，成为癌症发生的危险因素的观点。
