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| Status |
Public on Nov 30, 2011 |
| Title |
CCN5, a novel transcriptional repressor |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
We performed microarray gene expression profiling of one MCF-7-sh-CCN5 sample and one MCF-7-sh-scrambled sample (control sample).
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| Contributor(s) |
Sabbah M, Céline P, Ferrand N, Megalophounos V, Lambein K, De Wever O, Nazaret N, Lachuer J, Dumont S, Redeuilh G |
| Citation(s) |
21262769 |
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| Submission date |
Nov 17, 2010 |
| Last update date |
Oct 28, 2014 |
| Contact name |
Michèle SABBAH |
| E-mail(s) |
michele.sabbah@inserm.fr
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| Phone |
033149284693
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| Organization name |
INSERM U938
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| Street address |
184 rue du faubourg Saint-Antoine
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| City |
paris |
| ZIP/Postal code |
75012 |
| Country |
France |
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| Platforms (1) |
| GPL2895 |
GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA133785 |
| Supplementary data files not provided |
| Processed data included within Sample table |
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