c-Myc phosphorylation by PKCζ represses prostate tumorigenesis

• DOI: 10.1073/pnas.1221799110
• Publication Date: 2013-04-03T03:16:28Z
• Authors: Ji Young Kim; Tania Valencia; Shadi Abu-Baker; Juan Linares; Sang Jun Lee; Tomoko Yajima; Jing Chen; Alexey Eroshkin; Elias A. Castilla; Laurence M. Brill; Mario Medvedovic; Michael Leitges; Jorge Moscat; Maria T. Diaz-Meco
• Keywords: Male; 0303 health sciences; Blotting, Western; PTEN Phosphohydrolase; Computational Biology; Prostatic Neoplasms; Microarray Analysis; Real-Time Polymerase Chain Reaction; 3. Good health; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-myc; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Animals; Neoplasm Metastasis; Phosphorylation; Luciferases; Protein Kinase C

Studies showing reduced PKCζ expression or enzymatic activity in different types of human cancers support the clinical relevance as a tumor suppressor. However, vivo role and its mechanisms action prostate cancer remain unclear. Here we demonstrate that genetic inactivation mice results invasive carcinoma context phosphatase tensin homolog deficiency. Bioinformatic analysis gene-expression sets revealed increased c-Myc transcriptional PKCζ-inactive cells, which correlated with cell growth, invasion, metastasis. Interestingly, knockdown overexpression kinase-inactive mutant resulted enhanced proliferation invasion vitro through mRNA protein levels decreased Ser-373 phosphorylation c-Myc. Analysis samples demonstrated at knockout tumors. In xenograft studies by is critical event control Collectively, these establish an important suppressor regulator function cancer.