 Pax8 mutations lead to a decrease in the transcriptional activity of NUE.Another binding-site is the CRE, where the CREB binds, taking part in NIS transcription.In contrast, growth factors such as IGF-1 and TGF-β (which is induced by the BRAF-V600E oncogene) suppress NIS gene expression, not letting NIS localize in the membrane.