Protein kinase C-iota (PKC-\#953;), an atypical member of the PKC family of Ser/Thr kinases has been recognized as an oncogene (Pharmacol Res. 55:487-497, 2007). PKC-\#953; manifests its effects by targeting various aspects of cancer cells such as growth, invasion and survival. This research focuses on the role of PKC-\#953; in neuroblastoma cell proliferation. Furthermore, we investigate the effects of the novel PKC-\#953; inhibitor ICA-1 on a cell signaling pathway. Specifically, our hypothesis is that neuroblastoma cell proliferation is mediated via a PKC-\#953;/Cdk7/cdk2 cell signaling pathway. PKC-\#953; is located on the chromosome 3 at 3q26.2, the most common genomic amplicon identified by comparative genomic hybridization (Nat Genet.202:207-21116, 1998). Cdk7 is a part of the cyclin-dependent kinase activating kinase (CAK) complex. The prime function of Cdk7 is to regulate the cell cycle by phosphorylating cyclin-dependent kinases for cell cycle progression. Previous research has shown that PKC-\#953; phosphorylates and activates glioma Cdk7 (Cell Prolif. 35:23-36, 2002; Tissue and Cell 37:53-58, 2005). Immunoprecipation studies with BE(2)-C neuroblastoma cells confirmed that PKC-\#953; directly associates and phosphorylates Cdk7 on Thr170, thus proving the hypothesis. However, in the presence of ICA-1 phosphorylation of Cdk7 on Thr170 is inhibited. These results suggest that ICA-1 mediates its antiproliferative effects by inhibiting the PKC-\#953;/Cdk7/cdk2 proliferation pathway of neuroblastoma cells. Hence, our results emphasize the potential of ICA-1 as a novel chemotherapeutic agent.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-50.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009