Project description:This SuperSeries is composed of the following subset Series: GSE23135: Genome-wide analysis of time-dependent gene expression in MCF-10A cells treated with the EGFR-specific inhibitor gefitinib for 45 hours GSE23136: Genome-wide analysis of time-dependent gene expression in MCF-10HER-2 cells treated with the EGFR-specific inhibitor gefitinib for 45 hours GSE23139: Genome-wide analysis of time-dependent gene expression in MCF-10HER-2/E7 cells treated with the HER-2-specific inhibitor CP724,714 for 45 hours Refer to individual Series
Project description:Results of blocking EGFR kinase activity in MCF-10A cells by treatment with gefitinib and measuring gene expression as a function of time provides information as to what genes are regulated by EGFR in these nontransformed breast epithelial cells. MCF-10A cells were treated with the EGFR-specific small molecule kinase inhibitor gefitinib for 45 hours. Total RNA was collected every 3 hours from parallel cultures throughout the 45 hour duration of treatment and genome-wide analysis of expression was performed on RNA from each time point (total 16 time points, starting at 0 hours treatment).
Project description:Results of blocking activated EGFR/HER-2 heterodimer signaling in MCF-10HER-2 cells by treatment with gefitinib and measuring gene expression as a function of time provides information as to what genes are regulated by EGFR/HER-2 signaling in these breast epithelial cells that are transduced to overexpress the HER-2 oncogene and express transformed phenotypes. MCF-10HER-2 cells were treated with the EGFR-specific small molecule kinase inhibitor gefitinib for 45 hours. Total RNA was collected every 3 hours from parallel cultures throughout the 45 hour duration of treatment and genome-wide analysis of expression was performed on RNA from each time point (total 16 time points, starting at 0 hours treatment).
Project description:Genome-wide analysis of time-dependent gene expression in MCF-10A cells treated with the EGFR-specific inhibitor gefitinib for 45 hours
Project description:Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), induces substantial clinical responses for non-small cell lung cancer (NSCLC) cells harboring EGFR activating mutations, but most of them invariably develop resistance. By generating a gefitinib resistance (PC9GR) from a human NSCLC-derived drug sensitive cell line (PC9), we studied differences of transcription dynamics between them by the aid of a computational decoupling of hidden regulatory signals from time course gene expression profiles. Given a collection of transcription factors (TFs) and their regulatory targets, the method captured temporally-synchronized shifts in evolving expression of target genes sharing each TF regulatory unit, and drew underlying regulatory signals. The analysis identified sterol regulatory element binding protein 1 (SREBP-1) as a key regulatory agent that facilitates the maintenance of drug tolerance, involving transcription controls of a G1-specific cyclin dependent kinase inhibitor whose expression was specifically elevated in PC9, but in turn, reduced in PC9GR Gefitinib-resistance cell line (PC9GR) was established derived from lung adenocarcinoma cell line PC9. PC9 cells and PC9GR cells were treated with the four different conditions, control (No treatment), EGF-treatment, gefitinib-treatment, and both gefitinib and EGF-treatment. In each condition, the gene expression was measured at 26 time points during 24 hrs.
Project description:Results of blocking HER-2 kinase activity in MCF-10A cells by treatment with CP724,714 and measuring gene expression as a function of time provides information as to what genes are regulated by HER-2 in these nontransformed breast epithelial cells. MCF-10A cells were treated with the HER-2-specific small molecule kinase inhibitor CP724,714 for 45 hours. Total RNA was collected every 3 hours from parallel cultures throughout the 45 hour duration of treatment and genome-wide analysis of expression was performed on RNA from each time point (total 16 time points, starting at 0 hours treatment).
Project description:Results of blocking EGFR kinase activity in MCF-10A cells by treatment with gefitinib and measuring gene expression as a function of time provides information as to what genes are regulated by EGFR in these nontransformed breast epithelial cells.
Project description:Results of blocking the kinase function of the activated HER-2 oncogene in MCF-10HER-2 cells by treatment with CP724,714 and measuring gene expression as a function of time provides information as to what genes are regulated by HER-2 in these breast epithelial cells that express transformed phenotypes. MCF-10HER-2 cells were treated with the HER-2-specific small molecule kinase inhibitor CP724,714 for 45 hours. Total RNA was collected every 3 hours from parallel cultures throughout the 45 hour duration of treatment and genome-wide analysis of expression was performed on RNA from each time point (total 16 time points, starting at 0 hours treatment).
Project description:Results of blocking the activated HER-2 oncogene kinase activity in MCF-10HER-2/E7 cells by treatment with CP724,714 and measuring gene expression as a function of time provides information as to what genes are regulated by HER-2 in these transformed breast epithelial cells. MCF-10HER-2/E7 cells were treated with the HER-2-specific small molecule kinase inhibitor CP724,714 for 45 hours. Total RNA was collected every 3 hours from parallel cultures throughout the 45 hour duration of treatment and genome-wide analysis of expression was performed on RNA from each time point (total 16 time points, starting at 0 hours treatment).
Project description:Genome-wide analysis of time-dependent gene expression in MCF-10A cells treated with the HER-2-specific inhibitor CP724,714 for 45 hours