INTENDENTE GUIRALDES 2160, piso 2, C1428EGA - Capital Federal - Argentina
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ResumenInformación suministrada por el agente en SIGEVA
Breast cancer is the leading cause of cancer-related death in women. Positive outcomes can be attributed to success with targeting hormone receptors in hormone receptor-positive disease, however, a significant fraction develops resistance and progresses to metastatic disease. At the molecular level, perturbations of cell type-specific enhancers and their transcriptional programs play key roles in tumorigenesis. We have recently shown a non-canonical role for Argonaute1 (AGO1) as coactivator of ...Breast cancer is the leading cause of cancer-related death in women. Positive outcomes can be attributed to success with targeting hormone receptors in hormone receptor-positive disease, however, a significant fraction develops resistance and progresses to metastatic disease. At the molecular level, perturbations of cell type-specific enhancers and their transcriptional programs play key roles in tumorigenesis. We have recently shown a non-canonical role for Argonaute1 (AGO1) as coactivator of estrogen-induced enhancers. ChIP-seq analysis showed that AGO1 colocalizes with estrogen-responsive enhancers in MCF7 cells (ER+ breast cancer cell line) in an estrogen-dependent manner. Interestingly, coimmunoprecipitation assays showed that AGO1 interacts with ER upon estradiol treatment. AGO1 modulates the recruitment of ER onto induced-enhancers, activates enhancer transcription, enhances induced enhancer-promoter interactions and activates target promoters in response to E2. Overall, these results suggest that AGO1 plays a critical role during the activation estrogen-induced enhancers.