Project description:Our aim was to identify time-dependent changes in gene expression associated with Epidermal Growth Factor (EGF) and Hergulin B1 (HRG) stimulation of normal human mammary luminal epithelial cells (HB4a) and a derivative cell line (C3.6)overexpressing the receptor tyrosine kinase ErbB2/HER2. Serum-starved HB4a parental cells and ErbB2-overexpressing C3.6 cells were stimulated with EGF or HRG for 4 h, 18 h and 24 h or left unstimulated (0 h) prior to microarray analysis of mRNA levels of 9,932 probes, representing ~6,000 genes. Four replicates of each sample were co-hybridized to chips with a common RNA reference allowing direct comparison of gene expression across all experimental conditions: time, growth factor and cell line.

2006-08-15 | E-TABM-106 | biostudies-arrayexpress

Transcription profiling of human MCF7 cells after EGF, HRG stimulation

Project description:Sharing common ErbB/HER receptor signaling pathway, heregulin (HRG) induces differentiation of MCF-7 breast cancer cells while epidermal growth factor (EGF) elicits proliferation. Although the cell fate led by those two ligands was totally different, the gene expression profile in early transcription was unexpectedly qualitatively similar, suggesting that the gene expression in late transcription, not early transcription, may reflect a respect of ligand specificity. In this study, based on the data from time-course microarray of all human genes, we predicted and determined a series of transcription factors which may control HRG-specific timed-late transcription and cellular differentiation of MCF-7 cells. Validation analyses showed that one of activator protein 1 (AP-1) families appeared just after c-Fos expression, another AP-1 family partner, induced expression of another transcription factor through activation of AP-1 complex. Furthermore, expression of this transcription factors caused suppression of extracellular signal-regulated kinase (ERK) phosphorylation which is sustainedly regulated by HRG-initiated ErbB signaling. Overall, our analysis indicated an importance of formation of timed-transcriptional regulatory network and its function to control upstream signaling pathway through negative feedback for cellular differentiation. Experiment Overall Design: MCF7 human breast cancer cells were stimulated by the growth hormone (epidermal growth factor (EGF) or heregulin (HRG)). Control was set as non-treated cells.

2008-10-26 | E-GEOD-13009 | biostudies-arrayexpress

Molecular Atlas of HER2+ Breast Cancer Cells Stimulated with EGF and HRG: Temporal Insights into Mechanisms in Trastuzumab Resistance [ATAC-Seq]

Project description:Trastuzumab therapy in HER2+ breast cancer patients have mixed success owing to acquired resistance to therapy. In this study, we investigate the cellular mechanisms underlying acquired resistance using -sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG, across time. Our measurements probe early receptor organization through microscopy, signaling events through multi-omic measurements and assess the cellular energetic state through mitochondrial measurements. Our integrative analyses of these multimodal measurements highlight differential mechanisms in both cell lines in response to ligands. In BT474, an active PI3K-AKT-mTORC1 signaling contributes to an active mitochondrial bioenergetic state (glycolysis and lipid metabolism) for both ligands EGF and HRG. A HIF1A mediated increase in cellular bioenergetics is also seen. In BT474R, there is a ligand-dependent activation of signaling cascades. In EGF treated BT474R, an EGFR driven IRF1/STAT1/STAT2 activation with likely impact on cellular bioenergetics is seen, whilst an AR mediated alteration of lipid metabolism is pronounced after HRG treatment.

2024-02-14 | GSE237605 | GEO