| Glucose-regulated stresses confer resistance to VP-16 in human cancer cells through a decreased expression of DNA topoisomerase II. | |
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MedLine Citation:
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PMID: 8704275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucose-regulated proteins (GRPs) are induced in cells by a variety of stress conditions such as treatment with 2-deoxyglucose, glucosamine, or the calcium ionophore A23187. We found that resistance to topoisomerase II (topo II) inhibitors, VP-16 and adriamycin, was induced by these treatments in human colon cancer HT-29 cells. Similar VP-16 resistance occurred in human ovarian cancer A2780 and breast cancer MCF-7 cells. The VP-16 resistance was reversible, since the sensitivity of the cells to VP-16 recovered within 24 h after the stresses were removed. Western blotting analysis showed that under these stress conditions the cellular contents of topo II alpha were decreased. The decreased expression of topo II was reversed to control levels within 24 h following removal of the stresses. The decrease in topo II levels under the stress conditions correlated well with the induction of GRP78 and 94. The close correlation between topo II and GRPs suggests that topo II is a protein sensitive to the glucose-regulated stresses. Since hypoxia and nutrient deprivation, which are also GRP-inducing conditions, could occur naturally in the solid tumors, the stress-associated cellular resistance through decrease in topo II levels may be a mechanism of the natural resistance of the solid tumors to topo II-directed chemotherapy. |
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Authors:
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J Yun; A Tomida; K Nagata; T Tsuruo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology research Volume: 7 ISSN: 0965-0407 ISO Abbreviation: Oncol. Res. Publication Date: 1995 |
Date Detail:
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Created Date: 1996-09-06 Completed Date: 1996-09-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9208097 Medline TA: Oncol Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 583-90 Citation Subset: IM |
Affiliation:
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Laboratory of Biomedical Research, University of Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology* Calcimycin / pharmacology DNA Topoisomerases, Type II / antagonists & inhibitors* Deoxyglucose / pharmacology Drug Resistance Etoposide / pharmacology* HSP70 Heat-Shock Proteins / physiology* Humans Membrane Proteins / physiology* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/HSP70 Heat-Shock Proteins; 0/Membrane Proteins; 0/glucose-regulated proteins; 154-17-6/Deoxyglucose; 33419-42-0/Etoposide; 52665-69-7/Calcimycin; EC 5.99.1.3/DNA Topoisomerases, Type II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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