Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells
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Tumor cells often express elevated levels of heat-shock protein (HSP) 70. The present study was designed to invesitgate the role of HSP70 in the proliferation and survival of tumor cells in the human system. When Molt-4 and other tumor cells were treated in vitro with HSP70 antisense oligomer, they displayed propidiumiodide-stained condensed nuclei (intact or fragmented). A ladder-like pattern of DNA fragments was observed with HSP70 antisense-oligomer-treated tumor cells in agrose gel electrophoresis, which was consistent with internucleosomal DNA fragmentation. Flow cytometry analysis revealed the hypodiploid DNA peak of propidium-iodide-stained nuclei in the antisense-oligomer-treated cells. The apoptosis induced by HSP antisense oligomer was dose- and time-dependent. The antisense oligomer induced apoptosis mainly in tumor cells at G1 and S phase, resulting in an inhibition of cell proliferation. HSP70 antisense oligomer caused DNA-sequence-specific inhibition of HSP70 expression, which preceded apparent apoptosis. These results indicate that HSP70 antisense treatment inhibits the expression of HSP70, which in turn inhibits cell proliferation and induces apoptosis in tumor cells and suggest that HSP70 is required for tumor cells to proliferate and survive under normal condition.
Key wordsHeat-shock protein Tumor cells Apoptosis Proliferation
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- 6.Craig EA, Kramer J, Kosic-Smithers J (1987) SSC1, a member of the 70-kDa heat shock protein multigene family ofSaccharomyces cerevisiae, is essential for growth. Proc Natl Acad Sci USA 80:4156Google Scholar
- 7.Eastman A (1990) Activation of programmed cell death by anticancer agents: cisplatin as a model system. Cancer Cells (Cold Spring Harbor) 2:275Google Scholar
- 16.Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Sciences 259:1409Google Scholar
- 20.Uchida A and Fukata H (1993) Natural killer cell-derived granule protein: DNA fragmentation and apoptosis induced by framentin. Clin Immunol 25:646Google Scholar
- 25.Williams GT, Smith CA (1993) Molecular regulation of apoptosis: genetic control on cell death. Cell 54:777Google Scholar