Acta Pharmacologica Sinica (2010) 31: 347–354; doi: 10.1038/aps.2009.204

Acta Pharmacologica Sinica (2010) 31: 347–354; doi: 10.1038/aps.2009.204; published online 15 February 2010

Original Article

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

Xiao-ping ZHAO^{1, #}, Yong-yao HUANG^{2, #}, Yu HUANG¹, Ping LEI¹, Ji-lin PENG¹, Sha WU¹, Min WANG¹, Wen-han LI¹, Hui-fen ZHU¹, Guan-xin SHEN^{1, *}

¹Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; ²Department of Surgery, Hubei Hospital of Traditional Chinese Medicine, Wuhan 430074, China

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.

Keywords: transforming growth factor-β1; CXC chemokine receptor 4; stromal cell-derived growth factor-1α; breast cancer; metastasis

We thank Prof Zuo-hua FENG for valuable discussions and advice. We also thank Dr Jun-fa XU and Bao-jun HUANG for providing the pcDNA3.1-Fc plasmid. The study was supported by the 863 program of China (No 2006AA02Z158) and the Doctoral Fund of Ministry of Education of China (No 20060487024 and 20070487103).

^#The first two authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail guanxin_shen@yahoo.com.cn (Guan-xin SHEN).
Received 2009-09-01 Accepted 2009-12-28

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