UPK2 and in situ carcinoma: By comparison (though not presented/reviewed here), the UPII-SV40T transgenic mice mimics the non-papillary pathway with loss of tumor suppressors p53 and pRb functions to develop CIS, high-grade papillary tumors, and high-grade UCC co-existing with muscle-invasive UCC and/or metastasis [11,21].