Hypoxia is one of the major stress inducing factors that arises within solid tumors including breast tumors. A low oxygen condition stabilizes HIF-1a and HIF-2a and these can then dimerize with ARNT forming HIF-1 and HIF-2, which subsequently Pixantrone Maleate inhibitor modulate gene expression programs that effectively promote cell survival. The importance of chronic hypoxia on cancer cells is that this condition has been associated with the generation of aggressive phenotypes, chemo- and radiation resistance, and metastatic potential. Our recent studies have provided evidence that in breast cancer up-regulation of DDX3 expression can be associated with an aggressive phenotype and down-regulation or targeted inhibition of DDX3 can mitigate its actions. Whether DDX3 is a contributing factor to the aggressive phenotype of hypoxic cancer cells is not known and the question of transcriptional regulation of human DDX3 during hypoxia has not previously been addressed. Given this, it was pertinent to ask about the molecular mechanisms that might induce DDX3 expression in Thiazolidine inhibitor response to hypoxia. In the present study, we provide the first evidence that hypoxia induces the expression of DDX3 in human breast epithelial cells and moreover that this regulation is mediated in part by HIF-1 binding to HRE within the DDX3 promoter. The in vitro increase in the expression of DDX3 mRNA measured in both MCF 10A and MCF 7 cell lines following hypoxic treatment occurred in a time dependent manner and was transient. This is consistent with other reports that have shown that measured increases in mRNA expression during hypoxia can be dependent on the severity as well as duration of the treatment and the stability of an mRNA in a given cell line. For example, Guo et al. reported that the induction of the CYGB gene in response to hypoxia was instantaneous but the time that the maximum mRNA level was reached varied with the cell line and thus was found at 3 h in BEAS-2B cells and 6 h in HeLa cells. Maximum mRNA expression of DDX3 is observed in both cell lines tested here at 8 h of hypoxic treatment but in MCF 10A cells these levels declined at later time points, which was also the case during CoCl2 treatment of MCF 7 cells.