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Ca²?/calmodulin-dependent protein kinase II regulates the growth of human osteosarcoma cells in vivo

by Choo, Hyeran.

Abstract (Summary)
Osteosarcoma is the most predominant primary bone cancer among pediatric patients. The pathogenesis and mechanism of osteosarcoma, however, as yet remains unclear. This study investigated the hypothesis that Ca2+/calmodulin-dependent protein kinase II (CaMK II), activated by Ca2+ and its intracellular receptor, calmodulin, plays a critical role in the growth of human osteosarcoma cells. The inhibition of CaMK II with its pharmacologic antagonist KN-93 was used to investigate the role of CaMK II in the growth of human osteosarcoma cells because our preliminary data showed that ?-CaMK II is expressed in several human osteosarcoma cell lines. To examine the in vivo effects of KN-93 on human osteosarcoma cells, MG-63 cells and Saos-2 cells were subcutaneously inoculated in 5-week-old male athymic nude mice. The mice were then treated with either KN-93 or phosphate buffered saline every other day for 6 weeks. The tumor cells were also inoculated in the tibia of the mice at the same time when mice received subcutaneous inoculation. The final total volume of subcutaneous tumors of KN-93-treated group was 40% smaller in MG-63 cells and 41 % smaller in Saos-2 cells than that of each control group at sacrifice. Supporting these findings, micro-computerized tomography of mouse tibia where MG-63 cells were grown provided another line of evidence that pathologic bone formation by osteosarcoma cells was decreased by KN-93 treatment. Further, immunohistochemistry staining on these samples demonstrated that the expression of p21 was ii significantly increased while that of p-Rb was decreased in the KN-93-treated group. These results suggest that p21-involving signaling cascade mediated by CaMK II may be one of the potential mechanisms controlling the growth of human osteosarcoma cells, which will warrant further investigations aiming at a novel target to treat human osteosarcomas. iii
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School:University of Alabama at Birmingham

School Location:USA - Alabama

Source Type:Master's Thesis

Keywords:ca 2 calmodulin dependent protein kinase mice osteosarcoma inhibitors

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