Reference SummaryOster H, Cancer Res 2006 Jul 15;66(14):6955-63
Title |
Protein kinase C alpha but not PKCzeta suppresses intestinal tumor formation in ApcMin/+ mice. |
Authors |
Oster H; Leitges M |
Journal |
Cancer Res |
Volume |
66 |
Issue |
14 |
Year |
2006 |
Pages |
6955-63 |
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 PKCalpha and PKCzeta in colorectal cancer. Both isoforms were found to be strongly down-regulated in intestinal tumors of ApcMin/+ mice. A deletion of PKCzeta did not affect tumorigenesis in this animal model. In contrast, PKCalpha-deficient ApcMin/+ mice developed more aggressive tumors and died significantly earlier than their PKCalpha-proficient littermates. Even without an additional Apc mutation, PKCalpha 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. |
Links |
J:112117 – MGI References 16849539 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| 129S2/Sv | Intestine - Large Intestine - Colon polyp | Intestine - Large Intestine - Colon |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine - Large Intestine - Colon polyp | Intestine - Large Intestine - Colon |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| B6.129-ApcMin/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| B6.129-ApcMin/+ Prkcatm1Far | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| 129S2/Sv | Intestine - Small Intestine - Distal polyp | Intestine - Small Intestine - Distal |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine - Small Intestine - Distal polyp | Intestine - Small Intestine - Distal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6.129-ApcMin/+ | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6.129-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Distal tumor | Intestine - Small Intestine - Distal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Ileum tumor | Intestine - Small Intestine - Ileum |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Ileum tumor | Intestine - Small Intestine - Ileum |
observed |
||
| 129S2/Sv | Intestine - Small Intestine - Medial polyp | Intestine - Small Intestine - Medial |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine - Small Intestine - Medial polyp | Intestine - Small Intestine - Medial |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| B6.129-ApcMin/+ | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| B6.129-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Medial tumor | Intestine - Small Intestine - Medial |
observed |
||
| 129S2/Sv | Intestine - Small Intestine - Proximal polyp | Intestine - Small Intestine - Proximal |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine - Small Intestine - Proximal polyp | Intestine - Small Intestine - Proximal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6.129-ApcMin/+ | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6.129-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine - Proximal tumor | Intestine - Small Intestine - Proximal |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6;129S2-ApcMin/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6.129-ApcMin/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6.129-ApcMin/+ Prkcatm1Far | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| B6;129S2-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine adenoma | Intestine |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine adenoma | Intestine |
observed |
||
| B6;129S2-ApcMin/+ | Intestine adenoma - papillary | Intestine |
observed |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine carcinoma | Intestine |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine carcinoma | Intestine |
observed |
||
| 129S2/Sv | Intestine polyp | Intestine |
observed |
||
| 129S2/Sv-Prkcatm1Far | Intestine polyp | Intestine |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine tumor | Intestine |
observed |
||
| B6;129S2-ApcMin/+ | Intestine tumor | Intestine |
observed - 100 |
||
| B6;129S2-ApcMin/+ Prkcatm1Far | Intestine tumor | Intestine |
observed - 100 |
||
| B6;129S2-ApcMin/+ | Intestine tumor | Intestine |
observed |
||
| B6;129S2-ApcMin/+ Prkcztm1Jmos | Intestine tumor | Intestine |
observed |