The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells.

ABSTRACT

Osteosarcoma (OS) is a high-grade malignant bone tumor. In these studies, the cell apoptosis-related gene, programmed cell death 5 gene (PDCD5), and various fragments of it, were overexpressed in the OS cell line, MG-63. The effects of PDCD5 on MG-63 cells both in vivo and in vitro were then identified. Our results indicate that PDCD5 can induce apoptosis and G(2) phase arrest in MG-63 cells. Moreover, expression of PDCD5 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors that did not express PDCD5. To analyze the signaling pathway involved, western blotting was performed. In these assays, PDCD5 was found to inhibit the Ras/Raf/MEK/ERK signaling pathway, leading to inhibition of cyclin B and CDK1. In addition, down-regulation of ERK resulted in activation of caspase 3 and caspase 9. These results are consistent with the G(2) phase arrest observed with overexpression of PDCD5. However, a G(1) phase arrest was not observed. Therefore, proteins associated with the G(1) phase of the cell cycle were overexpressed in combination with PDCD5 overexpression. Overall, these studies demonstrate the anti-tumor activity of PDCD5 in the OS cell line, MG-63, and provide insight into relevant mechanisms that may lead to novel treatments for OS.