Retroviral Vector-Mediated Transfer of an Antisense Cyclin G1 Construct Inhibits Osteosarcoma Tumor Growth in Nude Mice
| Autor: | David R. Hinton, Erlinda M. Gordon, Nian-Ling Zhu, Gene Hung, Vernon T. Tolo, Michael J. Skotzko, Daniel S. Chen, W. French Anderson, Frederick L. Hall |
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| Rok vydání: | 1997 |
| Předmět: |
musculoskeletal diseases
Cyclin G1 Genetic enhancement Genetic Vectors Gene Expression Mice Nude Osteosarcoma Tumor Biology DNA Antisense Viral vector Cyclin G Mice Cyclins Tumor Cells Cultured Genetics Animals Humans Molecular Biology Cyclin Osteosarcoma Cell Cycle Gene Transfer Techniques Molecular biology Disease Models Animal Retroviridae Metastatic osteosarcoma Molecular Medicine Neoplasm Transplantation |
| Zdroj: | Human Gene Therapy. 8:1667-1674 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.1997.8.14-1667 |
| Popis: | Metastatic osteosarcoma is a potential target for gene therapy, because conventional therapies are only palliative and metastatic disease is invariably fatal. Overexpression of the cyclin G1 (CYCG1) gene is frequently observed in human osteosarcoma cells, and its continued expression is found to be essential for their survival. Previously, we reported that down-regulation of cyclin G1 protein expression induced cytostatic and cytocidal effects in human MG-63 osteosarcoma cells (Skotzko et al., Cancer Research, 1995). Here, we extend these findings in a tumorigenic MNNG/HOS cell line and report on the effective inhibition of tumor growth in vivo by an antisense cyclin G1 retroviral vector when delivered as concentrated high titer vector supernatants directly into rapidly growing subcutaneous tumors in athymic nude mice. Histologic sections from the antisense cyclin G1 vector-treated tumors showed decreased mitotic indices and increased stroma formation within the residual tumors. Furthermore, in situ analysis of the cell-cycle kinetics of residual tumor cells revealed a decrease in the number of cells in S and G2/M phases of the cell cycle concomittant with an accumulation of cells in the G1 phase. Taken together, these studies demonstrate in vivo efficacy of a high-titer antisense cyclin G1 retroviral vector in an animal model of osteosarcoma. |
| Databáze: | OpenAIRE |
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