SMAD3 and renal cell carcinoma: Moreover, there is evidence that estrogen receptor β (ERβ) could play a promoting role in RCC progression and that targeting the ERβ/TGF-β1/SMAD3 pathway with anti-estrogen ICI182,780 (Faslodex) or with a selective ERβ antagonist 4-[2-phenyl-5,7 bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol can significantly reduce RCC tumor growth and invasion (28).