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ELEVATED HSP70 STIMULATES CELL PROLIFERATION AND IS CYTOPROTECTIVE AGAINST HEAT AND VINCRISTINE TOXICITY IN MCF-7 CELLS.
Citation:
Barnes, J A., D J. Dix, B Collins, AND J W. Allen. ELEVATED HSP70 STIMULATES CELL PROLIFERATION AND IS CYTOPROTECTIVE AGAINST HEAT AND VINCRISTINE TOXICITY IN MCF-7 CELLS. Presented at American Association for Cancer Research Annual Meeting, San Francisco, CA, April 1-5, 2000.
Description:
Heat-shock proteins (HSPs) play important roles in regulating cell growth and protecting cells from adverse effects of heat and chemical stress. In many types of cancer, elevated HSP70 levels are associated with poor prognosis and resistance to chemotherapeutic agents. In the present study, we used a tetracycline-controlled gene expression system in human MCF-7 breast cancer cells to evaluate the effects of HSP70 overexpression on cell growth and resistance to hyperthermia and vincristine toxicity. HSP70 overexpressing cells exhibited faster doubling times as compared with non -overexpressing (control) cells (39 vs. 53 hrs.). Following hypertherria treatment (43?C for 30 or 60 min.), control cells underwent dose-dependent decreases in cell number which were not observed in HSP70 overexpressing cells. Ethidium bromide and acridine orange staining of heat-treated cells also revealed significant reductions in cell viability (p<.05) and increases in death (p<.05) and apoptosis in control vs. HSP70 overexpressing cells. A cytokinesis-block micronucleus (MN) assay with kinetochore staining was used to measure chromosome damage induced by vincristine. Again, cytoprotection in HSP70 overexpressing cells was evident; lower frequencies of vincristine-induced chromosome loss were observed in overexpressing vs. control cells. Overall, the data in this study provide further evidence linking HSP70 expression with increased cell proliferation and resistance to toxic effects from heat and chemotherapeutic agents.