HSP70 Overexpression Mediates the Escape of a Doxorubicin-Induced G2 Cell Cycle Arrest

The stress inducible heat shock protein 70 (hsp70) confers resistance to a variety of adverse environmental conditions including certain anticancer drugs. In the present study we explored cellular consequences of hsp70 overexpression with respect to genotoxic stress. Employing an isogenic set of sta...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1996-03, Vol.220 (1), p.153-159
Main Authors: Karlseder, Jan, Wissing, Dorte, Holzer, Gerhard, Orel, Lukas, Sliutz, Gerhard, Auer, Herbert, Jäättelä, Marja, Simon, Manuel M.
Format: Article
Language:English
Subjects:
Animals
Cell Cycle - physiology
Cell Line
Cell Survival - drug effects
DNA Damage
Doxorubicin - pharmacology
Drug Resistance - genetics
G2 Phase - drug effects
G2 Phase - genetics
G2 Phase - physiology
Gene Expression
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - physiology
Humans
Mice
Reactive Oxygen Species - metabolism
Transfection
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Summary:The stress inducible heat shock protein 70 (hsp70) confers resistance to a variety of adverse environmental conditions including certain anticancer drugs. In the present study we explored cellular consequences of hsp70 overexpression with respect to genotoxic stress. Employing an isogenic set of stable transfectant cells, one overexpressing hsp 70 and the other serving as control, we found that a high hsp70 expression level is sufficient to provide protection against the cytotoxicity of doxorubicin. In addition, hsp70-protected cells showed the capability to restart cell proliferation at concentrations where control cells arrested. However, the DNA lesion density was comparable in the lines used. Recording the cell cycle control revealed a dramatic shortening of the doxorubicin-mediated cell cycle arrest in the G2 phase upon hsp70 overexpression. Our data suggest an involvement of hsp70 in the regulation of the cell cycle.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1996.0373