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

Authors

Bilal B. Hafeez, The University of Texas Rio Grande ValleyFollow
Louise Meske
Ashok Singh
Anupama Singh
Weixiong Zhong
Patricia Powers
Manorama John
Anne E. Griep
Ajit K. Verma

Document Type

Article

Publication Date

4-20-2016

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 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.

Recommended Citation

Hafeez, B. B., Meske, L., Singh, A., Singh, A., Zhong, W., Powers, P., John, M., Griep, A. E., & Verma, A. K. (2016). Tissue-specific conditional PKCε knockout mice: a model to precisely reveal PKCε functional role in initiation, promotion and progression of cancer. Oncotarget, 7(22), 33069–33080. https://doi.org/10.18632/oncotarget.8850

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

Publication Title

Oncotarget

DOI

10.18632/oncotarget.8850

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology