ESR2 and renal cell carcinoma: We first established RCC cell lines with high or low ERβ level by overexpressing ERβ (oeERβ) in ccRCC A498 cells that have a lower endogenous ERβ expression, as well as by suppressing ERβ using shRNA (shERβ) in ccRCC 786-O cells that have a higher endogenous ERβ expression (Fig. 1a).