dc.contributor.author	Van Rooyen, Beverley A.
dc.contributor.author	Schafer, Georgia
dc.contributor.author	Leaner, Virna D.
dc.contributor.author	Parker, M. Iqbal
dc.date.accessioned	2014-02-07T08:52:51Z
dc.date.available	2014-02-07T08:52:51Z
dc.date.issued	2013-10
dc.date.updated	2013-10-07T15:08:28Z
dc.description	Please cite as follows:	en_ZA
dc.description	Van Rooyen, B. A., Schafer, G., Leaner, V. D. & Parker, M. I. 2013. Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner. Cell Communication and Signaling, 11(1):75, doi:10.1186/1478-811X-11-75.
dc.description	The original publication is available at http://www.biosignaling.com/content/11/1/75
dc.description.abstract	Background: Recent studies have revealed that interactions between tumour cells and the surrounding stroma play an important role in facilitating tumour growth and invasion. Stromal fibroblasts produce most of the extracellular matrix components found in the stroma. The aim of this study was to investigate mechanisms involved in tumour cell-mediated regulation of extracellular matrix and adhesion molecules in co-cultured fibroblasts. To this end, microarray analysis was performed on CCD-1068SK human fibroblast cells after direct co-culture with MDA-MB-231 human breast tumour cells. Results We found that the expression of both connective tissue growth factor (CTGF/CCN2) and type I collagen was negatively regulated in CCD-1068SK fibroblast cells under direct co-culture conditions. Further analysis revealed that Smad7, a known negative regulator of the Smad signalling pathway involved in CCN2 promoter regulation, was increased in directly co-cultured fibroblasts. Inhibition of Smad7 expression in CCD-1068SK fibroblasts resulted in increased CCN2 expression, while Smad7 overexpression had the opposite effect. Silencing CCN2 gene expression in fibroblasts led, in turn, to a decrease in type I collagen mRNA and protein levels. ERK signalling was also shown to be impaired in CCD-1068SK fibroblasts after direct co-culture with MDA-MB-231 tumour cells, with Smad7 overexpression in fibroblasts leading to a similar decrease in ERK activity. These effects were not, however, seen in fibroblasts that were indirectly co-cultured with tumour cells. Conclusion We therefore conclude that breast cancer cells require close contact with fibroblasts in order to upregulate Smad7 which, in turn, leads to decreased ERK signalling resulting in diminished expression of the stromal proteins CCN2 and type I collagen.	en_ZA
dc.description.version	Publishers' Version	en_ZA
dc.identifier.citation	Van Rooyen, B. A., Schafer, G., Leaner, V. D. & Parker, M. I. 2013. Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner. Cell Communication and Signaling, 11(1):75, doi:10.1186/1478-811X-11-75.	en_ZA
dc.identifier.issn	1478-811X (online)
dc.identifier.other	doi:10.1186/1478-811X-11-75
dc.identifier.uri	http://hdl.handle.net/10019.1/86119
dc.language.iso	en_ZA	en_ZA
dc.publisher	BioMed Central	en_ZA
dc.rights.holder	Beverley A van Rooyen et al.; licensee BioMed Central Ltd.	en_ZA
dc.subject	Tumor cells	en_ZA
dc.subject	Fibroblasts	en_ZA
dc.subject	Breast cancer	en_ZA
dc.title	Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner	en_ZA
dc.type	Article	en_ZA

Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner

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