Early growth response gene-1 and hypoxia-inducible factor-1α affect tumor metastasis via regulation of tissue factor. (May 2013)

• Record Type: Journal Article
• Authors: Sun, Li; Liu, Yang; Lin, Sensen; Shang, Jing; Liu, Jin; Li, Ji; Yuan, Shengtao; Zhang, Luyong
• Is Part Of: Acta oncologica. Volume 52:Number 4(2013)
• Page Start: 842
• Page End: 851
• Publication Date: 2013-05
• Subjects: Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.992
• DOI: 10.3109/0284186X.2013.705890
• Languages: English
• ISSNs: 0284-186X

Abstract

<abstract> <title>Abstract</title> <p> <italic>Background.</italic> Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. <italic>Material and methods.</italic> 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. <italic>Results</italic>. 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. <italic>Conclusions.</italic> 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.</p> </abstract>