Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
Project description:To investigate the oxidant sensitivity of E/ER regulated gene expression, E/ER regulated genes are identified using E deprivation or; ER-alpha siRNA knockdown; and oxidative stress responsive is determined by 8hr exposure to diamide, hydrogen peroxide and menadione Experiment Overall Design: MCF7 cells were treated under various conditions to identifiy oxidative stress responsive E/ER regulated genes. Association of these genes with respect to tumor phenotypes are assessed
Project description:These RNA-seq data were generated to correlate with genomic interaction data in a related Hi-C analysis. MCF10A is a normal-like mammary epithelial cell line and MCF7 is a transformed estrogen responsive breast cancer cell line derived from a metastatic site; both are commonly used in models of breast cancer progression. Analysis revealed a set of genes related to repression of WNT signalling that were both up-regulated in MCF7 and located in genomic regions that had transitioned from closed to open structure in MCF7. RNA-seq of MCF10A and MCF7 cells. 3 replicates each. Sequencing was strand-specific and conducted on ribo-depleted RNA.
Project description:These RNA-seq data were generated to correlate with genomic interaction data in a related Hi-C analysis. MCF10A is a normal-like mammary epithelial cell line and MCF7 is a transformed estrogen responsive breast cancer cell line derived from a metastatic site; both are commonly used in models of breast cancer progression. Analysis revealed a set of genes related to repression of WNT signalling that were both up-regulated in MCF7 and located in genomic regions that had transitioned from closed to open structure in MCF7.
Project description:The two estrogen receptors, ERα and ERβ function as ligand-inducible transcription factors. Most in vitro studies have reported that ERα drives breast cancer growth whereas ERβ, if expressed, suppresses growth. To dissect function and gene expression profile regulated by ERα or ERβ, respectively, we generated a novel cell model expressing only ERβ, by applying CRISPR-cas9 to delete ERα in MCF7 cells with stable Tet-Off-inducible ERβ expression. This model with ERβ expression only, exhibited regulation of known estrogen responsive genes in a ligand-dependent manner. By cell proliferation assay, we found that either ER was required for proliferation, and that while E2 increased proliferation of ERα (only) MCF7, it reduced proliferation of ERβ (only) MCF7 cells. RNA-Seq analysis revealed 768 and 984 specific target genes regulated by ERα and ERβ in response to E2, respectively. Furthermore, functional enrichment analysis showed that the two ER isoforms regulated cell proliferation in opposite direction. In conclusion, within the same cellular context the two ERs regulated cell proliferation in opposite manner by regulating distinct sets of target genes in response to E2. The novel developed cell model provides a novel and valuable resource to further complement the mechanistic understanding of the two different ER isoforms.