Function Of DEK Oncogene In Regulating The VEGF Expression And Tumor Angiogenesis

Tumor cells obtain nutrients through the blood vessels, and blood vessels also provide a channel for tumor metastasis. Tumor growth and metastasis can be inhibited by inhibiting tumor angiogenesis. Vascular endothelial growth factor(VEGF) is the most important regulator of tumor angiogenesis, a process essential for tumor growth and metastasis. The DEK oncogene is overexpressed in various cancers and overexpression of DEK correlates with poor clinical outcome. However, the function of DEK regulating tumor angiogenesis is still unclear. Our study showed that DEK oncogene regulated VEGF expression and tumor angiogenesis, which provided theoretical basis for cancer therapy.1. Effect of DEK oncogene on the expression of VEGF and its function in the regulation of angiogenesis The effect of DEK on the expression of VEGF was detected by luciferase activity, RT-PCR and the effect of DEK on cell growth, migration, and angiogenesis was observed. The results showed that DEK activates the transcription of VEGF, promotes the expression of VEGF, and promotes the growth, migration and angiogenesis of HUVEC cells.2. Effect of DEK on the biological activity of vascular endothelial cells by VEGF The effect of DEK on the growth, migration and angiogenesis of HUVEC cells was observed by neutralization of secreted VEGF by a VEGF neutralizing antibody. The results showed that DEK-mediated enhancement of VEGF expression in the conditioned medium is necessary for HUVEC proliferation, migration, and angiogenesis.3. Study on the correlation between DEK oncogene and HIF-1a in VEGF expression The effect of DEK on the expression of VEGF was detected by hypoxia and knockdown HIF-1α, and we tested the effect of the conditioned medium derived from knockdown HIF-1α stable breast cancer cell lines on HUVEC proliferation, migration and angiogenesis. The results showed that DEK regulated VEGF expression in HIF-1α-dependent and-independent manners.4. Study on the molecular mechanism of DEK oncogene in the regulation of VEGF We detedcted the DEK binding sites in VEGF promoter by EMSA and CHIP assay. DEK was recruited to the regions containing DEK responsive element(DRE) and HRE of VEGF promoter. HIF-1α was recruited to the regions containing HRE responsive element.5. Study on the relationship between DEK oncogene and HIF-1a Confirm the relationship between DEK and HIF-1a by GST pull-down and immunoprecipitation. Results showed that: under physiological conditions, DEK and HIF-1α interacted with each other.Conclusion: 1. The DEK oncogene affects angiogenesis by promoting VEGF expression; 2. The DEK oncogene can be combined with the VEGF promoter and activates VEGF expression in HIF-1a-dependent and –independent manners.