These changes were linked to perfusion deficits in solid tumors, which came from rapid tumor growth and profoundly disorganized vasculature. It has been suggested that the tumor microenvironment is a unique setting for tumor progression, which requires genetic adaptations in cancer cells for further survival and proliferation. Cell stresses induced by the microenvironment, especially hypoxia and reoxygenation, might cause these genetic changes. Regions of hypoxia are a common feature in solid tumors. Oxygen is a limiting factor because of the imbalance between O2 delivery and consumption. The O2 VE-821 deficiency is attributed to insufficient vasculatures and oxygen depletion in successive cell layers distal to the vessel lumen; simultaneously, there is an increase in O2 consumption due to the high metabolic rate of tumor cells. Many studies have reported that hypoxic tumors were more malignant and resistant to therapy, and thus had a worse prognosis. This phenomenon has been demonstrated in many tumor types. Moreover, the oxygen concentration within a hypoxic region is highly variable. Since tumor vasculatures are highly inefficient and unstable, red blood cells flux to the hypoxic regions, resulting in reperfusion or reoxygenation. Reoxygenation not only increases oxygen supply but also induces oxidative stress in the cells. This oxidative stress could cause damage to cellular macromolecules and lead to increased genomic instability. If tumor cells survive after exposure to hypoxia/reoxygenation insults, they may demonstrate increases in malignancy, DNA over-amplification, drug resistance, and metastatic potential. Cellular adaptation to hypoxia is well documented, but little is known about adaptive mechanisms to reoxygenation. Therefore, we used genome-wide expression microarrays to investigate the dynamics of transcriptional profiling during reoxygenation in MCF-7 breast cancer cells. Our microarray results showed that NMYC down-regulated gene 1 had the maximal response after reoxygenation. Therefore, we focused on investigating its functional role in reoxygenation. The functional assays revealed that cell migration of breast cancer cells during reoxygenation was driven by down-regulation of NDRG1. Lastly, the regulatory model of NDRG1 using in silico analysis was proposed for further investigation. Several studies have reported that tumor cells display increased drug resistance and metastatic potential after exposure to hypoxia/reoxygenation insults. Although cellular adaptations to hypoxia are well documented, little is known about adaptive mechanisms to reoxygenation. Here, we examined the dynamics of genome-wide gene expression during reoxygenation, and found that the differentially expressed genes were involved in the HIF-1-alpha transcription factor network and C-MYC transcriptional activation. In this study, principal component analysis of the oxygenresponsive genes showed high reproducibility over time. Based on the number of O2-responsive genes at different time points, the active period of transcription in response to reoxygenation appears to be between 8 and 12 hours.