Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling

• DOI: 10.1073/pnas.1007863107
• Publication Date: 2010-11-23T05:41:46Z
• Authors: Christine M. Fill...; Piyush B. Gupta; Jenny A. Rudnick; Silvia Caballero; Patricia J. Keller; Eric S. Lander; Charlotte Kuperwa...
• Keywords: Fibroblast Growth Factor 9; 0301 basic medicine; Breast Neoplasms; Estrogens; 3. Good health; Fibroblast Growth Factors; 03 medical and health sciences; Cell Line, Tumor; Paracrine Communication; Neoplastic Stem Cells; Humans; Receptor, Fibroblast Growth Factor, Type 3; Female; T-Box Domain Proteins; Signal Transduction

Many tumors contain heterogeneous populations of cells, only some which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer often termed “cancer stem cells” or stem-like (CSCs), rely upon developmental signaling pathways are important for survival expansion normal cells. Here we report that, in analogy embryonic mammary epithelial biology, estrogen expands the pool functional breast CSCs through a paracrine FGF/FGFR/Tbx3 pathway. Estrogen FGF9 pretreatment induced CSC properties cell lines freshly isolated whereas cotreatment cells with tamoxifen small molecule inhibitor FGFR was sufficient prevent estrogen-induced CSCs. Furthermore, reduction Tbx3 gene expression able abrogate tumorsphere formation, ectopic tumor seeding potential by 100-fold. These findings demonstrate stimulated pathway similarly controls biology.