Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells
| Autor: | Michèle Sabbah, Nathalie Ferrand, Gérard Redeuilh, Emilien Stragier |
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| Rok vydání: | 2012 |
| Předmět: |
Gene Expression
Breast Neoplasms Vimentin Biology Biochemistry Dexamethasone CCN Intercellular Signaling Proteins Breast cancer Glucocorticoid receptor Cell Line Tumor medicine Humans Neoplasm Invasiveness RNA Messenger RNA Neoplasm Promoter Regions Genetic skin and connective tissue diseases Glucocorticoids Molecular Biology DNA Primers Base Sequence Estradiol Estrogen Receptor alpha Cell Biology medicine.disease Hedgehog signaling pathway Repressor Proteins Cancer cell Cancer research biology.protein Female Signal transduction Estrogen receptor alpha Glucocorticoid Signal Transduction medicine.drug |
| Zdroj: | Biochemical Journal. 447:71-79 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial–mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients. |
| Databáze: | OpenAIRE |
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