Tissue-specific conditional PKCε knockout mice: a model to precisely reveal PKCε functional role in initiation, promotion and progression of cancer.
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 PKCε(LoxP/LoxP) mice have normal body weight and phenotype. To determine what effect loss of PKCε would have on the prostate, the PKCε(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 PKCε specifically in the prostate of PKCε-CKO mice. Histopathological analyses of prostate from both PKCε(LoxP/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, PKCε(LoxP/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 PKCε(LoxP/LoxP) mice will be useful for defining the link of PKCε to various cancers in specific organ, tissue, or cells.
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.
Bilal Bin
BB
Hafeez
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.
Louise
L
Meske
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.
Ashok
A
Singh
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.
Anupama
A
Singh
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.
Weixiong
W
Zhong
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.
Patricia
P
Powers
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.
Manorama
M
John
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.
Anne E
AE
Griep
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.
Ajit K
AK
Verma
D000818:Animals; D018450:Disease Progression; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051744:Protein Kinase C-epsilon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D051744:Protein Kinase C-epsilon
PKCεLoxP/LoxP mice; transgenic mice