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

X Zhao, Y Huang, Y Huang, P Lei, J Peng… - Acta Pharmacologica …, 2010 - nature.com
X Zhao, Y Huang, Y Huang, P Lei, J Peng, S Wu, M Wang, W Li, H Zhu, G Shen
Acta Pharmacologica Sinica, 2010nature.com
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 …
Abstract
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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