Endometrial cancer is the most commonly diagnosed gynaecological cancer, resulting in 2,000 new cases and 300 deaths per year.The normal endometrium undergoes regular cyclical changes involving the growth and proliferation of stromal and epithelial cells, as well as angiogenesis. There is increasing evidence that local renin angiotensin systems contribute to the regulation of tumour progression in the endometrium. The normal endometrium produces renin and angiotensin converting enzyme (ACE), measurable levels of Angiotensin (Ang) II and vascular endothelial growth factor (VEGF), a key angiogenic factor. Ample evidence demonstrates that low oxygen promotes the growth and spread of cancers, however it is unknown whether hypoxia is a key factor in endometrial cancer. Since some RAS components are regulated by low oxygen and the RAS itself stimulates hypoxia-regulated genes such as VEGF, we aimed to explore the link between hypoxia and the RAS in endometrial cancer. We tested this by culturing ECC-1 cells in one of three oxygen tensions (1%, 5% and 20% O2). We predicted that low oxygen would stimulate the pro-angiogenic Ang II/Ang II type 1 receptor (AT1R) RAS pathway and VEGF. We found that although low oxygen significantly increased the expression of VEGF, expression of the pro-angiogenic RAS pathways were suppressed, i.e., ACE1 was lower at 24 and 48 h incubation, and REN and the AT1R (AGTR1) was lower at 48 h incubation. Interestingly, ACE2 expression increased with low oxygen, despite it being part of the anti-angiogenic RAS pathway (P<0.05). Hypoxia generally stimulates angiogenesis and invasion, whereas we demonstrated that low oxygen suppressed the pro-angiogenic RAS pathway (AT1R), but up-regulated ACE2. This data suggests that hypoxia might be promoting differentiation of the cells into an invasive pathway; showing similar expression patterns of VEGF and AGTR1 to endometrial cancers of a higher grade and greater depth of myometrial invasion.