Original Article

Transforming growth factor-β1 upregulates the expression of CXC chemokine receptor 4 (CXCR4) in human breast cancer MCF-7 cells

Authors: Xiao-ping Zhao, Yong-yao Huang, Yu Huang, Ping Lei, Ji-lin Peng, Sha Wu, Min Wang, Wen-han Li, Hui-fen Zhu, Guan-xin Shen
DOI: 10.1038/aps.2009.204


Aim: To investigate whether rhTGF-β1 or a recombinant vector encoding a fusion protein comprising an extracellular domain of TGF-β receptor II and an IgG Fc fragment) affects the regulation of CXC chemokine receptor 4 (CXCR4) expression in MCF-7 human breast cancer cells.
Methods: MCF-7 breast cancer cells were treated with rhTGF-β1 or transfected with a recombinant vector, pIRES2-EGFP-TβRII-Fc. Expression of CXCR4 in these cells was then analyzed at the mRNA and protein levels by quantitative RT-PCR and flow cytometry assay, respectively. A transwell assay was used to measure the chemotactic response of these cells to SDF-1α.
Results: CXCR4 mRNA and protein expression were upregulated in TGF-β1-treated MCF-7 cells. These cells also demonstrated an enhanced chemotactic response to SDF-1α. In MCF-7 cells transiently transfected with pIRES2-EGFP-TβRII-Fc, a fusion protein named TβRII-Fc (approximately 41 kDa) was produced and secreted. In these transfected cells, there was a reduction in CXCR4 expression and in the SDF-1α-mediated chemotactic response.
Conclusion: TGF-β1 upregulated CXCR4 expression in MCF-7 cells, which subsequently enhanced the SDF-1α-induced chemotactic response. The results suggest a link between TGF-β1 and CXCR4 expression in MCF-7 human breast cancer cells, which may be one of the mechanisms of TGF-β1-mediated enhancement of metastatic potential in breast cancer cells.

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