Oncotarget

Research Papers:

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

Bilal Bin Hafeez _, Louise Meske, Ashok Singh, Anupama Singh, Weixiong Zhong, Patricia Powers, Manorama John, Anne E. Griep and Ajit K. Verma

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:33069-33080. https://doi.org/10.18632/oncotarget.8850

Metrics: PDF 1474 views  |   HTML 2267 views  |   ?  


Abstract

Bilal Bin Hafeez1, Louise Meske1, Ashok Singh1, Anupama Singh1, Weixiong Zhong2, Patricia Powers3, Manorama John3, Anne E. Griep4, Ajit K. Verma1

1Department 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

2Department 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

3University 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

4Department 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: PKCεLoxP/LoxP mice, transgenic mice

Received: February 12, 2016    Accepted: March 27, 2016    Published: April 20, 2016

ABSTRACT

PKCε is a transforming oncogene and a predictive biomarker of various human cancers. However, a precise in vivo link of PKCε to cancer induction, progression and metastasis remain undefined. To achieve these goals, we generated tissue specific conditional PKCε knockout mice (PKCε-CKO) using cre-lox technology. Homozygous PKCεLoxP/LoxP mice have normal body weight and phenotype. To determine what effect loss of PKCε would have on the prostate, the PKCεLoxP/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 PKCε specifically in the prostate of PKCε-CKO mice. Histopathological analyses of prostate from both PKCεLoxP/LoxP and prostate PKCε-CKO mice showed normal pathology. To determine the functional impact of prostate specific deletion of PKCε on prostate tumor growth, we performed an orthotopic xenograft study. Transgenic adenocarcinoma of the mouse prostate (TRAMP) cells (TRAMPC1, 2×106) were implanted in the prostate of PKCε-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 PKCε-CKO mice compared to wild type. To determine a link of PKCε to ultraviolet radiation (UVR) exposure-induced epidermal Stat3 phosphorylation, PKCεLoxP/LoxP mice were bred to tamoxifen-inducible K14 Cre mice. PKCε deletion in the epidermis resulted in inhibition of UVR-induced Stat3 phosphorylation. In summary, our novel PKCεLoxP/LoxP mice will be useful for defining the link of PKCε to various cancers in specific organ, tissue, or cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 8850