| First Author | Kim JY | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 16 | Pages | 6418-23 |
| PubMed ID | 23550155 | Mgi Jnum | J:196173 |
| Mgi Id | MGI:5486629 | Doi | 10.1073/pnas.1221799110 |
| Citation | Kim JY, et al. (2013) c-Myc phosphorylation by PKCzeta represses prostate tumorigenesis. Proc Natl Acad Sci U S A 110(16):6418-23 |
| abstractText | Studies showing reduced PKCzeta expression or enzymatic activity in different types of human cancers support the clinical relevance of PKCzeta as a tumor suppressor. However, the in vivo role of PKCzeta and its mechanisms of action in prostate cancer remain unclear. Here we demonstrate that the genetic inactivation of PKCzeta in mice results in invasive prostate carcinoma in vivo in the context of phosphatase and tensin homolog deficiency. Bioinformatic analysis of human prostate cancer gene-expression sets revealed increased c-Myc transcriptional activity in PKCzeta-inactive cells, which correlated with increased cell growth, invasion, and metastasis. Interestingly, PKCzeta knockdown or the overexpression of a kinase-inactive mutant resulted in enhanced cell proliferation and invasion in vitro through increased c-Myc mRNA and protein levels and decreased Ser-373 phosphorylation of c-Myc. Analysis of prostate cancer samples demonstrated increased expression and decreased phosphorylation of c-Myc at Ser-373 in PKCzeta knockout tumors. In vivo xenograft studies revealed that c-Myc phosphorylation by PKCzeta is a critical event in the control of metastasis. Collectively, these results establish PKCzeta as an important tumor suppressor and regulator of c-Myc function in prostate cancer. |
