Molecular Biotechnology Center (MBC); Department of Molecular Biotechnology and Health Sciences; University of Torino; Torino, Italy.
Cell Cycle. 2013 Aug 1;12(15):2409-22. doi: 10.4161/cc.25415. Epub 2013 Jun 28.
Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model.
了解癌症进展过程中的转录变化对于开发新的、更有效的诊断和治疗方法至关重要。众所周知，约 25%的人类浸润性乳腺癌中 ErbB2 过表达。我们之前已经证明，p130Cas 的过表达与 ErbB2 协同作用，促进乳腺细胞转化，并促进人乳腺上皮细胞三维（3D）培养物中 ErbB2 依赖性侵袭。在这里，我们通过比较编码和非编码基因表达谱，定义了与 p130Cas 过表达和 ErbB2 激活同时相关的侵袭特征在乳腺上皮细胞的 3D 培养物中。具体来说，我们发现参与氨基酸合成（CBS、PHGDH）、细胞运动、迁移（ITPKA、PRDM1）和血管生成（HEY1）的基因上调，而参与炎症反应（SAA1、S100A7）的基因下调。同时，我们还表明，特定 miRNA 的表达发生了改变。其中，miR-200b、miR-222、miR-221、miR-R210 和 miR-424 上调，而 miR-27a、miR-27b 和 miR-23b 下调。总的来说，这项研究首次揭示了 p130Cas 过表达在 ErbB2 转化的乳腺细胞模型中导致侵袭行为的基因表达变化。
