Two discrete single nucleotide polymorphisms (SNp. in the mammalian target of rapamycin ( mTOR ) promoter have been documented to form a risk allele for breast cancer, but the biology underlying this observation is poorly understood. In this study, Chen and colleagues perform molecular profiling of the rs2295079 and rs2295080 SNPs to determine their role in disease progression. They find that rs2295079, which constitutes a C G transversion at position -78 relative to the mTOR transcriptional start site, forms a de novo KLF5 binding motif in the mTOR promoter. Similarly, the rs2295080 SNP at position -141 consists of a G T transversion which constitutes an emergent ZEB1 binding site. Finally, the authors show that the -78G/-141T haplotype promotes breast cancer aggressiveness through upregulation of mTOR, which subsequently drives enhanced proliferation via cyclin D1 expression as well as resistance to paclitaxel via upregulation of the ABCB1 efflux pump.
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机译：两种离散的单一核苷酸多态性（SNP。已经记录了哺乳动物的哺乳动物靶标的靶标的乳腺癌的风险等位基因，但这种观察结果的生物学似乎很难理解。在这项研究中，陈和同事们进行分子分析 RS2295079和RS2295080的SNP，以确定它们在疾病进展中的作用。他们发现RS2295079相对于MTOR转录开始部位的CG转化，在MTOR启动子中形成DE Novo KLF5结合基质。同样， Love -141的RS2295080 SNP由GT转换组成，该GT转换构成出新的Zeb1结合位点。最后，作者表明，通过对mTOR的上调促进-78g / -141t单倍型促进乳腺癌侵蚀性，随后通过细胞周期蛋白D1推动增强的增殖 表达以及通过ABCB1 Efflux泵的上调抗紫杉醇的抗性。
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