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E-GEOD-25431 - CCN5, a novel transcriptional repressor

Status
Released on 30 November 2011, last updated on 7 December 2011
Organism
Homo sapiens
Samples (2)
Array (1)
Protocols (7)
Description
CCN5 is a member of the CCN (Connective Tissue Growth Factor/Cysteine-rich 61/Nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that CCN5 protein is localized mostly in the cytoplasm, and in part in the nucleus, of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor, presumably through association with histone deacetylase HDAC1. Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the TGF-beta signaling pathway, prominent among them TGF-betaRII receptor. We show that CCN5 is recruited to the TGF-betaRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-betaRII gene. Consistent with this finding, we found that CCN5 functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT. We performed microarray gene expression profiling of one MCF-7-sh-CCN5 sample and one MCF-7-sh-scrambled sample (control sample).
Experiment type
transcription profiling by array 
Contacts
Michèle SABBAH <michele.sabbah@inserm.fr>, Gérard Redeuilh, Joël Lachuer, Kathleen Lambein, Michèle Sabbah, Nathalie Ferrand, Nicolas Nazaret, Olivier De Wever, Prunier Céline, Sylvie Dumont, Virginie Megalophounos
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-25431.idf.txt
Sample and data relationshipE-GEOD-25431.sdrf.txt
Processed data (1)E-GEOD-25431.processed.1.zip
Array designA-GEHB-1.adf.txt
Links