Identification of Estrogen Response Element in Aquaporin-3 Gene that Mediates Estrogen-induced Cell Migration and Invasion in Estrogen Receptor-positive Breast Cancer.
Identification of Estrogen Response Element in Aquaporin-3 Gene that Mediates Estrogen-induced Cell Migration and Invasion in Estrogen Receptor-positive Breast Cancer.
复制标题
介导雌激素受体阳性乳腺癌细胞迁移和侵袭的 Aquaporin-3 基因中雌激素反应元件的鉴定
DOI：
10.1038/srep12484
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发表时间：
2015-07-29
影响因子：
4.6
通讯作者：
Sheng JZ
中科院分区：
文献类型：
--
作者：
Huang YT;Zhou J;Shi S;Xu HY;Qu F;Zhang D;Chen YD;Yang J;Huang HF;Sheng JZ
越来越多的证据表明，水通道蛋白（AQP）可能促进肿瘤的发展。连接AQPs病理功能的分子通路尚不清楚，需要更好地定义。本研究旨在探讨乳腺癌中高表达的水通道蛋白3（AQP 3）在雌激素受体（ER）阳性乳腺癌中的临床意义，并探讨AQP 3在雌激素相关乳腺癌进展中的调控机制。在这里，我们表明AQP 3是乳腺癌迁移和侵袭的重要执行者。我们首次报道了绝经前患者ER阳性乳腺癌组织中AQP 3表达高于绝经后患者。雌激素通过激活AQP 3基因启动子中的ERE直接上调AQP 3。AQP 3的上调可影响上皮-间质转化相关分子的表达和肌动蛋白-细胞骨架的重组，从而增强ER阳性乳腺癌细胞的迁移和侵袭能力。
Accumulating evidence suggests that aquaporins (AQPs) may facilitate tumor development. The molecular pathways connecting the pathological functions of AQPs are unclear and need to be better defined. This study aimed to investigate whether AQP3, one of the AQPs expressed highly in breast cancer, had any clinical implication in estrogen-receptor (ER) positive breast cancer and explore the regulatory mechanisms of AQP3 in estrogen-related breast cancer progression. Here we show that AQP3 is an important enforcer of migration and invasion in breast cancer. We, for the first time, reported that ER-positive breast cancer tissues obtained from premenopausal patients had higher AQP3 expression when compared to those obtained from postmenopausal patients. Estrogen directly upregulates AQP3 by activating ERE in the promoter of theAQP3gene. The upregulation of AQP3 can influence the expression of molecules related to epithelial-mesenchymal transition and the reorganization of actin-cytoskeleton, resulting in enhancement of cell migration and invasion in ER-positive breast cancer cells.