Tumor necrosis factor-α regulates expression of vascular endothelial growth factor via JNK and AP-1 pathway in MCF-7 cells

doi:10.3872/j.issn.1007-385X.2009.1.004

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Archive > Volume 16 Issue 1 > 2009,16(1):12-17. DOI:10.3872/j.issn.1007-385X.2009.1.004 Prev Next

Basic Research

Tumor necrosis factor-α regulates expression of vascular endothelial growth factor via JNK and AP-1 pathway in MCF-7 cells

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Abstract:

Objective: To investigate the mechanism by which tumor necrosis factorα (TNFα) induces expression of vascular endothelial growth factor(VEGF) in MCF7 cells. Methods: MCF7 cells were treated with TNFα (20 ng/ml) for different time periods. Western blotting was used to detect the phosphorylation of MAPK pathway proteins (JNK, P38, and ERK) and the expression and phosphorylation of AP1 family members(cJun，JunB，cFos，Fra1，Fra2，JunD). The activation of AP1 was detected by immunoprecipitation(IP). RTPCR and Western blotting were used to detect the VEGF mRNA and protein expression. The VEGF protein expression was also detected after pretreatment with inhibitor of MAPK. ChIP method was used to verify the binding of pcJun to the promoter region of VEGF. Results: TNFα activated AP1 through JNK signal pathway. AP1 existed in the form of pcJuncJun and pcJunJunB homodimer after activation. TNFα increased VEGF transcription by activating transcriptional factor AP1 and result in increased expression of VEGF protein. Pcjun regulated the transcription of VEGF through binding to the AP1 site of VEGF. Conclusion: TNFα can mediate the transcription of VEGF through a AP1dependent pathway.

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Supported by the National Natural Science Foundation of China(No.30772474); the Natural Science Foundation of Jiangsu Province (No. BK2008477)

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