Protein Kinase C α but not PKCζ Suppresses Intestinal Tumor Formation in ApcMin/+ Mice
Copyright policy )Protein Kinase C α but not PKCζ Suppresses Intestinal Tumor Formation in ApcMin/+ Mice
Abstract Members of the protein kinase C (PKC) family of serine/threonine kinases play key regulatory roles in numerous cellular processes, including differentiation and proliferation. Of the 11 mammalian PKC isoforms known, several have been implicated in tumor development and progression. However, in most cases, isotype specificity is poorly defined, and even contrary functions for a single PKC have been reported mostly because appropriate molecular and genetic tools were missing to specifically assess the contribution of single PKC isoforms in vivo. In this report, we therefore used PKC genetic targeting to study the role of PKCα and PKCζ in colorectal cancer. Both isoforms were found to be strongly down-regulated in intestinal tumors of ApcMin/+ mice. A deletion of PKCζ did not affect tumorigenesis in this animal model. In contrast, PKCα-deficient ApcMin/+ mice developed more aggressive tumors and died significantly earlier than their PKCα-proficient littermates. Even without an additional Apc mutation, PKCα knockout mice showed an elevated tendency to develop spontaneous intestinal tumors. Transcriptional profiling revealed a role for this kinase in regulating epidermal growth factor receptor (EGFR) signaling and proposed a synergistic mechanism for EGFR/activator protein and WNT/APC pathways in mediating intestinal tumor development. (Cancer Res 2006; 66(14): 6955-63)
- Max Planck Society Germany
- Hannover Medical School Germany
Mice, Knockout, Protein Kinase C-alpha, Epidermal Growth Factor, Transcription, Genetic, Gene Expression Profiling, Down-Regulation, Intestinal Polyps, ErbB Receptors, Mice, Inbred C57BL, Mice, Genes, jun, Animals, Intercellular Signaling Peptides and Proteins, Betacellulin, Colorectal Neoplasms, Protein Kinase C, Signal Transduction
Mice, Knockout, Protein Kinase C-alpha, Epidermal Growth Factor, Transcription, Genetic, Gene Expression Profiling, Down-Regulation, Intestinal Polyps, ErbB Receptors, Mice, Inbred C57BL, Mice, Genes, jun, Animals, Intercellular Signaling Peptides and Proteins, Betacellulin, Colorectal Neoplasms, Protein Kinase C, Signal Transduction
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