Journal article
Response of Cyclin B1 to Ionizing Radiation: Regulation by NF-Î B and Mitochondrial Antioxidant Enzyme MnSOD
Anticancer research, Vol.24, pp.2657-2663
01/01/2004
PMCID: PMC4139107
PMID: 15517870
Abstract
Background: To understand the molecular response of tumor cells to therapeutic ionizing radiation (IR), we previously reported that human breast cancer cells derived following chronic exposure to fractionated ionizing radiation (MCF+FIR) showed a transient radioresistance. MCF+FIR cells also demonstrated increased activity of NF-kappaB, increased expression of the mitochondrial antioxidant enzyme (MnSOD), and increased expression of a cell cycle regulatory protein (Cyclin B1). The present studies were designed to determine the relationship of NF-kappaB, MnSOD and Cyclin B1 expression in cellular adaptive responses to ionizing radiation.
Materials and methods: The first intron of the cyclin B1 gene with a putative NF-kappaB element was cloned into the pGL3 luciferase reporter (pGL3CB1EI1). PGL3CB1EI1 and control NF-kappaB luciferase activities were determined in MCF-7 and MCF+FIR cells treated with a single dose of radiation, over expression of the dominant negative mutant IkB (mIkB) or over expression of the SOD2 gene.
Results: MCF+FIR cells derived from fractionated IR demonstrated increased transactivation of the pGL3CB1EI1 and NF-kappaB controlled reporter activities, relative to the parental cell line. Transfection of dominant negative mutant IkB that inhibits NF-kappaB nuclear translocation, inhibited pGL3CB1EI1 and NF-kappaB activity, indicating the NF-kappaB dependence of pGL3CB1EI1 mediated transcription. In addition, over expression of the human SOD2 gene (MnSOD) inhibited NF-kappaB and pGL3CB1EI1 activity, indicating that superoxide or some species derived from superoxide may have participated in the up-regulation of reporter activity in response to chronic exposure to fractionated ionizing radiation. These results provide evidence suggesting that a signaling pathway involving NF-kappaB and Cyclin B1 may contribute to adaptive radioresistance induced by chronic exposure to fractionated IR and support the conclusion that MnSOD appears to be a negative regulator of this pathway.
Details
- Title: Subtitle
- Response of Cyclin B1 to Ionizing Radiation: Regulation by NF-Î B and Mitochondrial Antioxidant Enzyme MnSOD
- Creators
- MUNETAKA Ozeki - Radiation Biology, Division of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010 Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, 1-21-24, Kagoshima, Japan 890-0065 Free Radical and Radiation Biology, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, IA 52242, U.S.ADANIEL Tamae - Radiation Biology, Division of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010 Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, 1-21-24, Kagoshima, Japan 890-0065 Free Radical and Radiation Biology, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, IA 52242, U.S.ADE-XING Hou - Radiation Biology, Division of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010 Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, 1-21-24, Kagoshima, Japan 890-0065 Free Radical and Radiation Biology, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, IA 52242, U.S.ATIELI Wang - Radiation Biology, Division of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010 Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, 1-21-24, Kagoshima, Japan 890-0065 Free Radical and Radiation Biology, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, IA 52242, U.S.ATHOMAS Lebon - Radiation Biology, Division of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010 Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University, Korimoto, 1-21-24, Kagoshima, Japan 890-0065 Free Radical and Radiation Biology, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, IA 52242, U.S.ADOUGLAS R. Spitz - University of IowaJIAN JIAN LI - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Anticancer research, Vol.24, pp.2657-2663
- PMID
- 15517870
- PMCID
- PMC4139107
- ISSN
- 0250-7005
- eISSN
- 1791-7530
- Language
- English
- Date published
- 01/01/2004
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984313082902771
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