Upstream signaling experimentation in VHL-mutant RCC 786-O cells which have sustained HIF-2α protein expression revealed that estrogen receptor (Erβ) upregulates HIF-2α mRNA and protein through hypothesized transcriptional regulation at the HIF-2α promoter, suggesting partial dependence on the ER-pathway [68]. Here, ESR2 is linked to renal cell carcinoma.