Article

Transactivation of MCP-1/CCL2 by beta-catenin/TCF-4 in human breast cancer cells.

Laboratory of Developmental and Tumour Biology, University of Liège, Liège, Belgium.
International Journal of Cancer (impact factor: 5.44). 02/2006; 118(1):35-42. DOI:10.1002/ijc.21291 pp.35-42
Source: PubMed

ABSTRACT The loss of E-cadherin expression and the translocation of beta-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, beta-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the beta-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/beta-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with beta-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against beta-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the beta-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression.

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Keywords

beta-catenin binds
 
beta-catenin/TCF pathway
 
beta-catenin/TCF/LEF pathway
 
breast tumour cells
 
breast tumour progression
 
BT549 breast cancer cells transfected
 
E-cadherin expression
 
E-cadherin/beta-catenin complexes
 
epithelial cells
 
invasive breast cancer cells
 
MCP-1 expression correlates
 
MCP-1 mRNA
 
MCP-1 mRNA level
 
MCP-1 promoter
 
metastatic conversion
 
monocyte chemotactic protein-1
 
noninvasive breast cancer cell lines
 
potential regulation
 
T-cell factor/ lymphoid enhancer factor
 
TCF-4 cDNAs