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: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 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:Genome-wide analysis of time-dependent gene expression in MCF-10HER-2 cells treated with the EGFR-specific inhibitor gefitinib for 45 hours
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
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:Microarrays were used to analyze differential gene expression and to help determine the efficacy of Iressa (gefitinib), a tyrosine kinase inhibitor, on endometrial cancer cells. Type I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGFor gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade. Type I (Ishikawa H cells) and type II (Hec50co) derived endometrial carcinomas, were dosed with either EGF(epidermal growth factor) or Iressa (gefitinib) for 12 or 24 hours and gene expression was examined.
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.
