| First Author | Hafeez BB | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 6 | Pages | 2318-27 |
| PubMed ID | 21406403 | Mgi Jnum | J:169919 |
| Mgi Id | MGI:4943595 | Doi | 10.1158/0008-5472.CAN-10-4170 |
| Citation | Hafeez BB, et al. (2011) Genetic Ablation of PKC Epsilon Inhibits Prostate Cancer Development and Metastasis in Transgenic Mouse Model of Prostate Adenocarcinoma. Cancer Res 71(6):2318-27 |
| abstractText | Protein kinase C epsilon (PKCepsilon), a novel PKC isoform, is overexpressed in prostate cancer (PCa) and correlates with disease aggressiveness. However, the functional contribution of PKCepsilon to development or progression of PCa remained to be determined. Here we present the first in vivo genetic evidence that PKCepsilon is essential for both the development and metastasis of PCa in the transgenic mouse model of prostate adenocarcinoma (TRAMP). Heterozygous or homozygous genetic deletions of PKCepsilon in FVB/N TRAMP inhibited PCa development and metastasis as analyzed by positron emission tomography/computed tomography, tumor weight determinations, and histopathology. We also examined biomarkers associated with tumor progression in this model, including markers of survival, proliferation, angiogenesis, inflammation, and metastatic progression. To find clues about the genes regulated by PKCepsilon and linked to the Stat3 signaling pathway, we carried out focused PCR arrays of JAK/STAT signaling in excised PCa tissues from PKCepsilon wild-type and nullizygous TRAMP mice. Notably, PKCepsilon loss was associated with significant downregulation of proliferative and metastatic genes C/EBPbeta (CCAAT/enhancer binding protein beta), CRP (C-reactive protein), CMK, EGFR (epidermal growth factor receptor), CD64, Jun B, and gp130. Taken together, our findings offer the first genetic evidence of the role of PKCepsilon in PCa development and metastasis. PKCepsilon may be potential target for prevention and/or treatment of PCa. Cancer Res; 71(6); 2318-27. (c)2011 AACR. |
