Tissue-specific conditional PKCε knockout mice: a model to precisely reveal PKCε functional role in initiation, promotion and progression of cancer.

// Bilal Bin Hafeez 1 , Louise Meske 1 , Ashok Singh 1 , Anupama Singh 1 , Weixiong Zhong 2 , Patricia Powers 3 , Manorama John 3 , Anne E. Griep 4 , Ajit K. Verma 1 1 Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA 2 Department of Pathology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA 3 University of Wisconsin Biotechnology Center, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA 4 Department of Cell and Regenerative Biology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA Correspondence to: Ajit K. Verma, email: akverma@wisc.edu Keywords: PKCe LoxP/LoxP mice, transgenic mice Received: February 12, 2016     Accepted: March 27, 2016     Published: April 20, 2016 ABSTRACT PKCe is a transforming oncogene and a predictive biomarker of various human cancers. However, a precise in vivo link of PKCe to cancer induction, progression and metastasis remain undefined. To achieve these goals, we generated tissue specific conditional PKCe knockout mice (PKCe-CKO) using cre-lox technology. Homozygous PKCe LoxP/LoxP mice have normal body weight and phenotype. To determine what effect loss of PKCe would have on the prostate, the PKCe LoxP/LoxP mice were bred to probasin cre (PB-Cre4 + ) mice which express cre specifically in the prostate epithelium of postnatal mice. Western blot and immunohistochemical analyses showed reduced levels of PKCe specifically in the prostate of PKCe-CKO mice. Histopathological analyses of prostate from both PKCe LoxP/LoxP and prostate PKCe-CKO mice showed normal pathology. To determine the functional impact of prostate specific deletion of PKCe on prostate tumor growth, we performed an orthotopic xenograft study. Transgenic adenocarcinoma of the mouse prostate (TRAMP) cells (TRAMPC1, 2×10 6 ) were implanted in the prostate of PKCe-CKO mice. Mice were sacrificed at 6th week post-implantation. Results demonstrated a significant (P<0.05) decrease in the growth of TRAMPC1 cells-derived xenograft tumors in PKCe-CKO mice compared to wild type. To determine a link of PKCe to ultraviolet radiation (UVR) exposure-induced epidermal Stat3 phosphorylation, PKCe LoxP/LoxP mice were bred to tamoxifen-inducible K14 Cre mice. PKCe deletion in the epidermis resulted in inhibition of UVR-induced Stat3 phosphorylation. In summary, our novel PKCe LoxP/LoxP mice will be useful for defining the link of PKCe to various cancers in specific organ, tissue, or cells.