The Liggins Institute, The University of Auckland, Auckland, New Zealand.
Mol Cancer Res. 2010 Mar;8(3):444-56. doi: 10.1158/1541-7786.MCR-09-0368. Epub 2010 Mar 2.
Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5alpha in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5alpha was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5alpha in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of beta-CATENIN at cell-cell junctions and with altered mRNA expression of mesenchymal markers in mammary carcinoma cells. In addition, forced expression of PAX5alpha in MCF-7 and MDA-MB-231 cells significantly reduced cell migration and invasion. Concomitantly, small interfering RNA-mediated depletion of PAX5alpha increased MCF-7 total cell number, cell motility, migration, and invasion. These studies show that PAX5alpha enhances the epithelial characteristics of mammary carcinoma cells, reminiscent of mesenchymal to epithelial transition.
PAX5 表达失调与转移性乳腺癌有关，尽管 PAX5 在癌症进展中的确切作用尚不清楚。PAX5alpha 在乳腺癌细胞系 MCF-7 和 MDA-MB-231 中的稳定强制表达降低了细胞周期进程、细胞存活和锚定非依赖性细胞生长。在异种移植研究中，PAX5alpha 的强制表达与肿瘤体积的显著减少相关。此外，在乳腺癌细胞中强制表达 PAX5alpha 导致细胞形态发生改变，从而增强了上皮细胞特征。形态变化与细胞间连接处的 β-CATENIN 定位以及乳腺癌细胞中间充质标记物的 mRNA 表达改变有关。此外，在 MCF-7 和 MDA-MB-231 细胞中强制表达 PAX5alpha 显著降低了细胞迁移和侵袭。同时，小干扰 RNA 介导的 PAX5alpha 耗竭增加了 MCF-7 细胞总数、细胞迁移、迁移和侵袭。这些研究表明，PAX5alpha 增强了乳腺癌细胞的上皮特征，类似于间充质到上皮的转变。
