Transfection of a human topoisomerase II alpha gene into etoposide-resistant human breast tumor cells sensitizes the cells to etoposide
| Autor: | T, Asano, T, An, L A, Zwelling, H, Takano, A T, Fojo, E S, Kleinerman |
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| Rok vydání: | 1996 |
| Předmět: |
Amsacrine
Cell Death Cell Cycle Breast Neoplasms Transfection Antineoplastic Agents Phytogenic Drug Resistance Multiple DNA-Binding Proteins Isoenzymes Mice DNA Topoisomerases Type II Antigens Neoplasm Doxorubicin Drug Resistance Neoplasm Tumor Cells Cultured Animals Humans Female RNA Messenger Cell Division Etoposide |
| Zdroj: | Oncology research. 8(3) |
| ISSN: | 0965-0407 |
| Popis: | The etoposide-resistant human breast cancer cell line MDA-VP was derived from MDA-parent cells by sequential selection in increasing concentrations of etoposide. MDA-VP cells express a lower amount of topoisomerase II alpha mRNA than the MDA-parent does, have mutations in topoisomerase II alpha (topo II) cDNA, and show cross-resistance to doxorubicin and amsacrine. We investigated whether transfer of a normal human topoisomerase II alpha (H-topo II) gene into MDA-VP cells could overcome their resistance to etoposide. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus (MMTV) promoter (pMAMneo) was transfected into MDA-VP cells (MDA-VP-hTOP2MAM). These H-topo II-transfected cells showed increased H-topo II mRNA expression and protein levels compared with MDA-VP parental cells or with MDA-VP cells transfected with the control pMAM vector (MDA-VP-MAM). Following cell exposure to dexamethasone, DNA-protein cleavable complex formation and cytotoxicity induced by etoposide, doxorubicin, and amsacrine were increased in the MDA-VP-hTOP2MAM cells compared with MDA-VP-MAM cells. However, these changes were short-lived, and by 24 h, cytotoxicity, cleavable DNA-protein complex formation, and H-topo II protein levels returned to baseline values. These results indicate that sensitivity of MDA-VP cells correlated with changes in cellular H-topo II. The gene transfer of a normal H-topo II gene can sensitize MDA-VP cells to the actions of multiple antineoplastic agents that target topo II. |
| Databáze: | OpenAIRE |
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