PEA3 activates CXCL12 transcription in MCF-7 breast cancer cells

doi:10.3877/cma.j.issn.1674-0807.2011.04.012

中华乳腺病杂志(电子版) ›› 2011, Vol. 05 ›› Issue (04) : 474 -485. doi: 10.3877/cma.j.issn.1674-0807.2011.04.012

实验研究

PEA3 activates CXCL12 transcription in MCF-7 breast cancer cells

CHEN Li¹, CHEN Bo-bin², LI Jun-jie¹, JIN Wei¹, SHAO Zhi-min¹^,^†(

)

1.Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University
2.Department of Hematology,Huashan Hospital, Fudan University

收稿日期:2011-04-29 出版日期:2011-08-01
通信作者: SHAO Zhi-min
基金资助:
Foundation projects: The work was supported by the grants from National Natural Science Foundation of China (No.81072166); Innovation Program of Shanghai Municipal Education Commission (No. 09ZZ04); the Natural Science Foundation of Science and Technology Commission of Shanghai Municipality (No. 09ZR1406900); Shanghai Pujiang Program (2008)

Received:2011-04-29 Published:2011-08-01

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Objective

To explore the activity of PEA3 (polyomavirus enhancer activator 3 ) on CXCL12 (Chemokine CXC motif ligand 12) transcription and to reveal the role of PEA3 involved in CXCL12-mediated metastasis and angiogenesis in breast cancer.

Methods

Methods such as cell transfection, ChIP assay (chromatin immunoprecipitation),and siRNA (small interfering RNA) were applied to demonstrate and confirm the interaction between PEA3 and CXCL12.

Results

Over-expression of PEA3 could increase the CXCL12 mRNA level and the CXCL12 promoter activity in human MCF-7 breast cancer cells. ChIP assay demonstrated that PEA3 could bind to the CXCL12 promoter in the cells transfected with PEA3 expression vector. PEA3 siRNA decreased CXCL12 promoter activity and the binding of PEA3 to the CXCL12 promoter in MCF-7 cells.

Conclusions

PEA3 could activate CXCL12 promoter transcription. It may be a potential mechanism of tumor angiogenesis and metastasis regarding of PEA3 and CXCL12.

关键词: polyomavirus enhancer activator 3 (PEA3), chemokine CXC motif ligand 12 (CXCL12) promoter, transcription regulation

Fig 1 Overexpression of PEA3 induced CXCL12 mRNA level in MCF-7 cells

Fig 2 PEA3 activated CXCL12 promoter activity in MCF-7 cells

Fig 3 PEA3 bound to the CXCL12 promoter after overexpression of PEA3 in MCF-7 cells

Fig 4 PEA3 siRNA inhibited PEA3 and CXCL12 mRNA in MCF-7 cells

Fig 5 PEA3 siRNA repressed CXCL12 promoter activity in MCF-7 cells

Fig 6 PEA3 siRNA attenuated the binding of PEA3 to the CXCL12 promoter

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