title: HSP70 overexpression mediates the escape of a doxorubicin-induced G2 cell cycle arrest.
abstract: 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 hsp70 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.
authors.affiliation: Center of Applied Genetics, Univ. BOKU Vienna, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Karlseder
authors.forename: D
authors.initials: D
authors.lastname: Wissing
authors.forename: G
authors.initials: G
authors.lastname: Holzer
authors.forename: L
authors.initials: L
authors.lastname: Orel
authors.forename: G
authors.initials: G
authors.lastname: Sliutz
authors.forename: H
authors.initials: H
authors.lastname: Auer
authors.forename: M
authors.initials: M
authors.lastname: Jäättelä
authors.forename: M M
authors.initials: MM
authors.lastname: Simon
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
chemical_list: D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D004317:Doxorubicin