Institute of Cardiology, Lithuanian University of Health Sciences, 15 Sukilėlių Ave., LT- 50162, Kaunas, Lithuania.
Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296, Göteborg, Sweden.
Sci Rep. 2017 Aug 10;7(1):7820. doi: 10.1038/s41598-017-08329-8.
A comparative analysis between cancer cell lines and healthy dividing cells was performed using data (289 microarrays and 50 RNA-seq samples) from 100 different cancer cell lines and 6 types of healthy stem cells. The analysis revealed two large-scale transcriptional events that characterize cancer cell lines. The first event was a large-scale up-regulation pattern associated to epithelial-mesenchymal transition, putatively driven by the interplay of the SP1 transcription factor and the canonical Wnt signaling pathway; the second event was the failure to overexpress a diverse set of genes coding membrane and extracellular proteins. This failure is putatively caused by a lack of activity of the AP-1 complex. It was also shown that the epithelial-mesenchymal transition was associated with the up-regulation of 5 enzymes involved in the degradation of branched chain amino acids. The suitability of silencing one of this enzymes (branched chain amino acid transaminase 2; BCAT2) with therapeutic effects was tested experimentally on the breast cancer cell line MCF-7 and primary cell culture of breast tumor (BCC), leading to lower cell proliferation. The silencing of BCAT2 did not have any significant effect on ASM and MCF10A cells, which were used as models of healthy dividing cells.
对 100 种不同的癌细胞系和 6 种健康干细胞的 289 个微阵列和 50 个 RNA-seq 样本的数据进行了比较分析。分析揭示了两个特征性的大规模转录事件，第一个事件是与上皮-间充质转化相关的大规模上调模式，可能是由 SP1 转录因子和经典 Wnt 信号通路的相互作用驱动的；第二个事件是未能过度表达一组多样化的编码膜和细胞外蛋白的基因。这种失败可能是由于 AP-1 复合物缺乏活性所致。研究还表明，上皮-间充质转化与参与降解支链氨基酸的 5 种酶的上调有关。通过实验在乳腺癌细胞系 MCF-7 和乳腺癌原代细胞培养物 (BCC) 上测试了沉默其中一种酶（支链氨基酸转氨酶 2；BCAT2）的治疗效果，导致细胞增殖降低。沉默 BCAT2 对 ASM 和 MCF10A 细胞没有任何显著影响，这两种细胞被用作健康分裂细胞的模型。
