| First Author | Hafeez BB | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 22 | Pages | 33069-80 |
| PubMed ID | 27102301 | Mgi Jnum | J:314542 |
| Mgi Id | MGI:6827123 | Doi | 10.18632/oncotarget.8850 |
| Citation | Hafeez BB, et al. (2016) Tissue-specific conditional PKCepsilon knockout mice: a model to precisely reveal PKCepsilon functional role in initiation, promotion and progression of cancer. Oncotarget 7(22):33069-80 |
| abstractText | PKCepsilon is a transforming oncogene and a predictive biomarker of various human cancers. However, a precise in vivo link of PKCepsilon to cancer induction, progression and metastasis remain undefined. To achieve these goals, we generated tissue specific conditional PKCepsilon knockout mice (PKCepsilon-CKO) using cre-lox technology. Homozygous PKCepsilon(LoxP/LoxP) mice have normal body weight and phenotype. To determine what effect loss of PKCepsilon would have on the prostate, the PKCepsilon(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 PKCepsilon specifically in the prostate of PKCepsilon-CKO mice. Histopathological analyses of prostate from both PKCepsilon(LoxP/LoxP) and prostate PKCepsilon-CKO mice showed normal pathology. To determine the functional impact of prostate specific deletion of PKCepsilon on prostate tumor growth, we performed an orthotopic xenograft study. Transgenic adenocarcinoma of the mouse prostate (TRAMP) cells (TRAMPC1, 2x106) were implanted in the prostate of PKCepsilon-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 PKCepsilon-CKO mice compared to wild type. To determine a link of PKCepsilon to ultraviolet radiation (UVR) exposure-induced epidermal Stat3 phosphorylation, PKCepsilon(LoxP/LoxP) mice were bred to tamoxifen-inducible K14 Cre mice. PKCepsilon deletion in the epidermis resulted in inhibition of UVR-induced Stat3 phosphorylation. In summary, our novel PKCepsilon(LoxP/LoxP) mice will be useful for defining the link of PKCepsilon to various cancers in specific organ, tissue, or cells. |
