The KRAS-variant and its impact on normal breast epithelial cell biology.

摘要: MicroRNA (miRNA)-binding site variants in 3' untranslated regions (3'UTRs) are a novel class of germ-line, functional mutations, which now recognized as powerful biomarkers human cancer risk and biology. The first mutation discovered this is the KRAS-variant, let-7-binding 3'UTR KRAS oncogene. KRAS-variant predicts increased for certain populations, predictive biomarker treatment response across types, leads to conserved tumor biology elevated AKT signaling patient tumors, was recently found predict TGF-β immunosuppression patients. Based on patients, here we chose investigate altered normal cellular presence through interrogation an isogenic breast epithelial cell line model with without KRAS-variant. We find that cells exhibit mesenchymal phenotype, appears be due numerous molecular changes, including miRNA dysregulation autocrine pathway alterations, TGF-β, resulting ZEB SNAIL upregulation. Our findings support hypothesis has fundamental biological impact biology, these patients when they develop cancer.