Most solid tumors develop regions of low oxygen tension because of an imbalance in oxygen supply and consumption due to uncontrolled cell growth and insufficient vascularization [5] and [6]. Clinical and experimental evidence suggests that
EGFR 985-996 tumor hypoxia is associated with malignancy and the lack of response to cancer treatment [7]. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia [8]. HIF-1 is a heterodimeric complex composed of the hypoxia-inducible HIF-1α subunit and the constitutively expressed HIF-1β subunit. Under normoxic conditions, HIF-1α generally undergoes proteasomal degradation, but in hypoxic conditions, it is stabilized and translocated to the nucleus. HIF-1 binds to the specific sequence motif called the hypoxia response
element (HRE) in the promoter region of hypoxia response genes, including glycolytic enzymes, vascular endothelial growth factor (VEGF), and chemokine receptor CXCR4 [5] and [9]. Although HIF-1-dependent transcriptional activity is regulated by various signaling pathways, the effect of IFNγ on the hypoxia-induced HIF-1-dependent transcription remains to be determined.
