title: Role of inducible heat shock protein 70 in radiation-induced cell death.
abstract: We previously demonstrated the protective effect of inducible heat shock protein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth rate of inducible hsp70-transfected cells was 2-3 hours slower than that of control cells. Flow cytometric analysis of cells at G1 phase synchronized by serum starvation also showed the growth delay in the Hsp70-overexpressing cells. In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells, which were probably responsible for the reduction of cell growth. To find out if inducible Hsp70-mediated growth delay affected radiation-induced cell cycle regulation, flow cytometric and molecular analyses of cell cycle regulatory proteins and their kinase were performed. The radiation-induced G2/M arrest was found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced cyclin A or B1 expressions together with their kinase activities were also inhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apoptosis. When treated with nocodazole, radiation-induced mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase arrest, subsequently resulting in inhibition of radiation-induced cell death.
authors.affiliation: Laboratory of Radiation Effect, Korea Cancer Center Hospital, Seoul.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: S A
authors.initials: SA
authors.lastname: Choi
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: H Y
authors.initials: HY
authors.lastname: Chung
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.forename: C K
authors.initials: CK
authors.lastname: Cho
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D011233:Precipitin Tests; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C493957:Cdkn1a protein, mouse; D019925:Cyclin A; D019926:Cyclin B; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018840:HSP70 Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase