BACKGROUND: Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. MATERIAL AND METHODS: To verify the role of Egr-1 in hypoxia-induced TF expression in breast cancer cells, quantitative PCR and Western blot analysis were performed. The secretion of VEGF under hypoxia was detected by enzyme-linked immunosorbent assay (ELISA). Egr-1 and HIF-1α siRNA were transiently transfected into breast cancer cells to evaluate their specific roles. RESULTS: The increased Egr-1 expression occurring in hypoxic breast cancer cells can up-regulate TF expression and stimulating protein 1(Sp1) was not responsible for the hypoxia-induced expression of TF. HIF-1α mediated the hypoxia-induced up-regulation of TF expression through vascular endothelial growth factor (VEGF). The regulatory effects of Egr-1 on TF under hypoxia were independent of HIF-1α. Either Egr-1 or HIF-1α was responsible for hypoxic induction of tumor cells adhesion. HIF-1α, but not Egr-1, had a pivotal role in human breast cancer cells invasion. Both Egr-1 and HIF-1α were critical to angiogenesis induced by hypoxic conditions in MDA-MB-231 and HUVEC co-cultures. In nude mice, both Egr-1 and HIF-1α small interfering RNA (siRNA) could decrease extravasation of MDA-MB-435 cells in the lung after tail vein injection. CONCLUSIONS: Hypoxia-induced expression of TF in human breast cancer cells depends on Egr-1 and HIF-1α, and both of these proteins may play an important role in breast cancer metastasis, either directly or indirectly through the TF pathway.
BACKGROUND:Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. MATERIAL AND METHODS: To verify the role of Egr-1 in hypoxia-induced TF expression in breast cancer cells, quantitative PCR and Western blot analysis were performed. The secretion of VEGF under hypoxia was detected by enzyme-linked immunosorbent assay (ELISA). Egr-1 and HIF-1α siRNA were transiently transfected into breast cancer cells to evaluate their specific roles. RESULTS: The increased Egr-1 expression occurring in hypoxic breast cancer cells can up-regulate TF expression and stimulating protein 1(Sp1) was not responsible for the hypoxia-induced expression of TF. HIF-1α mediated the hypoxia-induced up-regulation of TF expression through vascular endothelial growth factor (VEGF). The regulatory effects of Egr-1 on TF under hypoxia were independent of HIF-1α. Either Egr-1 or HIF-1α was responsible for hypoxic induction of tumor cells adhesion. HIF-1α, but not Egr-1, had a pivotal role in humanbreast cancer cells invasion. Both Egr-1 and HIF-1α were critical to angiogenesis induced by hypoxic conditions in MDA-MB-231 and HUVEC co-cultures. In nude mice, both Egr-1 and HIF-1α small interfering RNA (siRNA) could decrease extravasation of MDA-MB-435 cells in the lung after tail vein injection. CONCLUSIONS:Hypoxia-induced expression of TF in humanbreast cancer cells depends on Egr-1 and HIF-1α, and both of these proteins may play an important role in breast cancer metastasis, either directly or indirectly through the TF pathway.
Authors: He Li; Yixiang Deng; Zhen Li; Ander Dorken Gallastegi; Christos S Mantzoros; Galit H Frydman; George E Karniadakis Journal: PLoS Comput Biol Date: 2022-03-07 Impact factor: 4.779
Authors: Magdalena L Bochenek; Rajinikanth Gogiraju; Stefanie Großmann; Janina Krug; Jennifer Orth; Sabine Reyda; George S Georgiadis; Henri M Spronk; Stavros Konstantinides; Thomas Münzel; John H Griffin; Philipp Wild; Christine Espinola-Klein; Wolfram Ruf; Katrin Schäfer Journal: JCI Insight Date: 2022-07-22