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首页> 外文期刊>Journal of Cellular Physiology >Characterization of WWOX inactivation in murine mammary gland development
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Characterization of WWOX inactivation in murine mammary gland development

机译：在小鼠表征WWOX失活乳腺发育

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The WW domain-containing oxidoreductase (WWOX) is commonly inactivated in multiple human cancers, including breast cancer. Wwox null mice die prematurely precluding adult tumor analysis. Nevertheless, aging Wwox-heterozygous mice at C3H genetic background develop higher incidence of mammary tumors. We recently generated a Wwox conditional knockout mouse in which loxp sites flank exon 1 in the Wwox allele and showed that total ablation of WWOX in these mice resembles that of conventional targeting of Wwox. Here, we report the characterization of WWOX ablation in mouse mammary gland using MMTV-Cre transgenic line. We demonstrated that WWOX ablation leads to impaired mammary ductal growth. Moreover, targeted deletion of WWOX is associated with increased levels of fibronectin, a component of the extracellular matrix. In addition, we showed that shRNA knockdown of WWOX in MCF10A breast epithelial cells dramatically increased fibronectin and is associated with enhanced cell survival and impaired growth in three-dimensional culture Matrigel assay. Taken together our results are consistent with a critical role for WWOX in normal breast development and tumorigenesis.
机译：WW domain-containing的氧化还原酶(WWOX)通常在多种人类癌症,灭活包括乳腺癌。过早地阻碍成人肿瘤分析。然而,老化Wwox-heterozygous小鼠的影响遗传背景开发的发生率更高乳腺肿瘤。条件敲除老鼠loxp网站侧面Wwox基因外显子1和显示在这些老鼠像总WWOX消融传统的针对Wwox。报告WWOX消融的表征使用MMTV-Cre转基因小鼠乳腺线。乳腺导管增长受损。删除WWOX与目标纤连蛋白水平上升的一个组成部分细胞外基质。WWOX的shRNA击倒MCF10A乳房上皮细胞显著增加纤连蛋白和增强细胞有关生存和增长的三维受损文化基底膜基质试验。结果是一致的一个重要的角色在正常乳房发育和WWOX肿瘤发生。

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