To test whether ISG15 contributes to tumorigenesis in vivo, we examined the ability of the ZR-75-1 breast cancer cells constitutively overexpressing ISG15 (ZR/control shRNA) and ZR-75-1 cells silenced for ISG15 expression (ZR/ISG15 shRNA), described in [13, 20], to form tumors in nude mice (Ncrnu/nu, Jackson Laboratory). Here, ISG15 is linked to breast carcinoma.