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Series GSE11888 Query DataSets for GSE11888
Status Public on Apr 27, 2009
Title Mutational analysis of progesterone receptor delineates different sets of regulated genes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Steroid hormone receptors act directly in the nucleus over the chromatin organization and transcriptional activity of several cellular promoters. On the other hand, they have an indirect effect on cytoplasmic signal transduction pathways, including MAPK, impacting ultimately on gene expression. We are interested on distinguishing between direct effects of progesterone receptor (PR) and those mediated by signal transduction pathways on transcription of hormone-responsive genes and cell proliferation. For this, we have stably expressed in a PR-negative breast cancer cell line, tagged forms of the PR isoform B mutated at regions involved either in DNA binding (DBD), or in its ability to interact with estrogen receptor and activate the c-Src/MAPK/Erk/Msk cascade (ERID). Both mutants impair PR-mediated activation of a well-understood model promoter in response to progestin, as well as hormone-induced cell proliferation. Additional mutants affecting transactivation activity of PR (AF2) or a Zn-finger implicated in dimerization (D-box) have also been tested. Microarrays and gene expression experiments in these cell lines define the subsets of hormone-responsive genes regulated by the different modes of action of PRB, as well as genes where the nuclear and nongenomic pathways of PRB cooperate. Correlation between CCND1 expression in the different PR mutants expressing cell lines and their ability to support hormone-induced cell proliferation, confirms CCND1 as a key controller gene.
 
Overall design A customized human cDNA microarray containing 826 genes of interest in breast cancer or steroid hormone regulation was used to identify subsets of genes that retain response to progestin in cells expressing defective PRB variants. Previous kinetic experiments performed with T47D cells on this array platform have shown that at 6 h of R5020 treatment, an extensive number of genes change its expression, being a compromise between rapid and long-term effects of this hormone on gene expression (unpublished results). TYML cells containing the empty vector, WT PRB, AF2, DBD and ERID, and T47D parental cells were serum-starved for 24 h and hormone (10 nM R5020) or vehicle-treated for 6 h. Cells were collected and RNA was extracted for microarray hybridization.
 
Contributor(s) Quiles I, Jordan A, Minana B, Ballare C, Beato M, Millan-Ariño L, Subtil A
Citation(s) 19299443
Submission date Jun 26, 2008
Last update date Mar 19, 2012
Contact name BELEN MINANA
E-mail(s) belen.minana@crg.es
Phone 0034933160276
Organization name Center for genomic regulation
Department GENE REGULATION, STEM CELLS AND CANCER
Lab REGULATION OF ALTERNATIVE SPLICING
Street address dr aiguader 88
City barcelona
State/province barcelona
ZIP/Postal code 08003
Country Spain
 
Platforms (1)
GPL5953 CRG Human Breast Cancer Array v4.0-0.8K
Samples (25)
GSM300110 T47D_MTVL_EtOH_6h_ReplicateA_73
GSM300113 T47D_MTVL_EtOH_6h_ReplicateB_74
GSM300143 T47D_MTVL_R5020_6h_ReplicateA_75
Relations
BioProject PRJNA105711

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11888_RAW.tar 7.9 Mb (http)(custom) TAR (of GPR, TXT)
Processed data included within Sample table

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