Receptor Biology Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States.
Reprod Toxicol. 2012 Dec;34(4):512-21. doi: 10.1016/j.reprotox.2012.08.005. Epub 2012 Aug 31.
ERΔ3 transgenic mice expressing a dominant negative estrogen receptor α (ERα) variant lacking the second zinc finger in the DNA binding domain were developed to examine its potential to inhibit estrogen action in vivo. To investigate if ERΔ3 expression influences uterine carcinogenesis, ERΔ3 transgenic mice were exposed to diethylstilbestrol (DES) on post-natal days 1-5. Neonatal DES treatment induced uterine adenocarcinomas in 81% of 8-month-old ERΔ3 mice compared to 49% of wild-type females (p<0.016). ERΔ3 did not inhibit the expression of the estrogen-responsive progesterone receptor and lactoferrin genes in the presence of ERα or modify their expression in ERα knockout (αERKO) mice. Higher circulating 17β-estradiol levels and non-classical signaling by ERΔ3 may be related to the earlier incidence of uterine cancer. These findings indicate that expression of this ERα variant can influence determining events in uterine cancer development and its natural occurrence in the human uterus would unlikely be protective.
为了研究 ERΔ3 表达是否会影响子宫癌的发生，将 ERΔ3 转基因小鼠在出生后第 1-5 天暴露于己烯雌酚（DES）下。与野生型雌性小鼠（p<0.016）相比，新生期 DES 处理诱导 8 月龄 ERΔ3 小鼠发生子宫腺癌的比例为 81%。在存在 ERα 的情况下，ERΔ3 并未抑制雌激素反应性孕激素受体和乳铁蛋白基因的表达，也未改变其在 ERα 敲除（αERKO）小鼠中的表达。较高的循环 17β-雌二醇水平和 ERΔ3 的非经典信号可能与子宫癌的更早发生有关。这些发现表明，这种 ERα 变体的表达可能会影响子宫癌发展的决定性事件，并且其在人类子宫中的自然发生不太可能具有保护作用。
