In the RCC cell lines including Caki-2 (from a primary tumor) and SK-RC-52 (from a metastatic tumor) IGF-1 was shown to enhance transforming growth factor-β (TGF-β) signaling and via TGF-β raise IGF-binding protein 3 (IGFBP-3) levels with growth-promoting effect [51]. This evidence concerns the gene IGFBP3 and renal cell carcinoma.