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Temporal Patterns of Mammary Epithelial Cell Gene Expression in Response to Glucocorticoid Receptor Activation

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Final rept. 15 May 2001-14 May 2002

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Because GR-mediated transcriptional regulation is required for the potent survival signal observed in MECs we hypothesized that the identification of key targets of GR-activation may lead to novel targets for breast cancer therapy. One approach to hone in on physiologically relevant genes is to analyze multiple time points for gene induction and repression by dexamethasone using microchip technology. This approach successfully allowed us to monitor gene expression at successive times in cells undergoing apoptosis in response to serum withdrawal and compare this set of genes to those expressed over time in cells protected from apoptosis by GTL activation, The concept to be tested was that we might efficiently identify relevant pathways involved in this novel survival signaling pathway by using cluster analysis to examine temporal patterns of expression rather than by simply cataloguing individual genes induced in an array at a single time point following CR activation. We achieved this goal using affymetrix chips and monitoring gene expression over or under baseline 30 minutes, 2 hours 4 hours and 24 hours following GR activation. Several of the gene products we identified are players in key signal transduction pathways involved in cell survival.

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  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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