Transforming Growth Factor-Beta 1 Upregulates The Expression Of Cxc Chemokine Receptor 4 (Cxcr4) In Human Breast Cancer Mcf-7 Cells

Aim: To investigate whether rhTGF-beta 1 or a recombinant vector encoding a fusion protein comprising an extracellular domain of TGF-beta 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-beta 1 or transfected with a recombinant vector, pIRES2-EGFP-T beta RII-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-1 alpha.Results: CXCR4 mRNA and protein expression were upregulated in TGF-beta 1-treated MCF-7 cells. These cells also demonstrated an enhanced chemotactic response to SDF-1 alpha. In MCF-7 cells transiently transfected with pIRES2-EGFP-T beta RII-Fc, a fusion protein named T beta RII-Fc (approximately 41 kDa) was produced and secreted. In these transfected cells, there was a reduction in CXCR4 expression and in the SDF-1 alpha-mediated chemotactic response.Conclusion: TGF-beta 1 upregulated CXCR4 expression in MCF-7 cells, which subsequently enhanced the SDF-1 alpha-induced chemotactic response. The results suggest a link between TGF-beta 1 and CXCR4 expression in MCF-7 human breast cancer cells, which may be one of the mechanisms of TGF-beta 1-mediated enhancement of metastatic potential in breast cancer cells.