Engineering Transcription Factors in Breast Cancer Stem Cells

摘要: Breast cancers are classified in at least six different subtypes (normal-like, luminal A, B, Her2, basal-like, claudin-low), which characterized by distinct genome-wide transcriptional profiles and response to therapy [1]. Recently, it has been shown that these intrinsic types of breast associated with unique DNA-methylation patterns [2,3,4]. In 2009, a large-scale genomic analysis cancer cohorts identified novel subtype enriched putative stem-cell (CSC) markers, named claudin-low [5]. addition or stem cell signatures, tumors Epithelial-to-Mesenchymal transition (EMT) such as high expression the Transcription Factors (TFs) Twist Snail, loss epithelial junction proteins, cadherins, claudins ocludins. Together basal-like cancers, carcinomas mostly triple negative, hence their lack Estrogen Receptor (ER), Progesterone (PR) Her2. Consequently, refractory regimens treat anti-estrogens conventional chemotherapy. Similarly serious ovarian also appear be poorly differentiated, grade, poor clinical outcome. These serous tumors, type II, often p53 BRCA mutations [6]. Thus, there is need develop more effective strategies target differentiated carcinomas. This will begin better understanding molecular pathways activated maintain aberrant proliferation potentially, tumor initiation. Little known regarding determinants initiation progression cancers. proposed originated oncogenic transformation bipotent progenitor cells, respectively. Consistent this idea, we found many normally expressed both, adult embryonic cells (hESCs), over-expressed first part chapter overview TFs TF networks could play role maintaining selfrenewal, special focus on OCT4-SOX2-NANOG network. abnormal reactivation TFs, suppressor genes undergo epigenetic silencing