This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, T. Articles by Li, J. J. Search for Related Content PubMed PubMed Citation Articles by Wang, T. Articles by Li, J. J.

The Role of Peroxiredoxin II in Radiation-Resistant MCF-7 Breast Cancer Cells

¹ Department of Chemistry, California State University, Carson, California; ² Department of Medical Oncology and ³ Division of Immunology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California; and ⁴ Division of Molecular Radiobiology, Purdue University School of Health Sciences, West Lafayette, Indiana

Requests for reprints: Tieli Wang, Department of Chemistry, California State University, Carson, CA 90072. Phone: 310-243-3388; Fax: 310-243-2593; E-mail: tilly{at}coh.org.

Although several signaling pathways have been suggested to be involved in the cellular response to ionizing radiation, the molecular basis of tumor resistance to radiation remains elusive. We have developed a unique model system based upon the MCF-7 human breast cancer cell line that became resistant to radiation treatment (MCF+FIR30) after exposure to chronic ionizing radiation. By proteomics analysis, we found that peroxiredoxin II (PrxII), a member of a family of peroxidases, is up-regulated in the radiation-derived MCF+FIR3 cells but not in the MCF+FIS4 cells that are relatively sensitive to radiation. Both MCF+FIR3 and MCF+FIS4 cell lines are from MCF+FIR30 populations. Furthermore, the resistance to ionizing radiation can be partially reversed by silencing the expression of PrxII by PrxII/small interfering RNA treatment of MCF+FIR3 resistant cells, suggesting that PrxII is not the sole factor responsible for the resistant phenotype. The relevance of this mechanism was further confirmed by the increased radioresistance in PrxII-overexpressing MCF+FIS4 cells when compared with vector control cells. The up-regulation of the PrxII protein in radioresistant cancer cells suggested that human peroxiredoxin plays an important role in eliminating the generation of reactive oxygen species by ionizing radiation. The present finding, together with the observation that PrxII is also up-regulated in response to ionizing radiation in other cell systems, strengthens the hypothesis that the PrxII antioxidant protein is involved in the cellular response to ionizing radiation and functions to reduce the intracellular reactive oxygen species levels, resulting in increased resistance of breast cancer cells to ionizing radiation.

This article has been cited by other articles:

				I.-S. Song, S.-U. Kim, N.-S. Oh, J. Kim, D.-Y. Yu, S. M. Huang, J.-M. Kim, D.-S. Lee, and N.-S. Kim Peroxiredoxin I contributes to TRAIL resistance through suppression of redox-sensitive caspase activation in human hepatoma cells Carcinogenesis, July 1, 2009; 30(7): 1106 - 1114. [Abstract] [Full Text] [PDF]

				Y. Miura, M. Kano, M. Yamada, T. Nishine, S. Urano, S. Suzuki, T. Endo, and T. Toda Proteomic Study on X-irradiation-responsive Proteins and Ageing: Search for Responsible Proteins for Radiation Adaptive Response J. Biochem., August 1, 2007; 142(2): 145 - 155. [Abstract] [Full Text] [PDF]

				M.-H. Kweon, V. M. Adhami, J.-S. Lee, and H. Mukhtar Constitutive Overexpression of Nrf2-dependent Heme Oxygenase-1 in A549 Cells Contributes to Resistance to Apoptosis Induced by Epigallocatechin 3-Gallate J. Biol. Chem., November 3, 2006; 281(44): 33761 - 33772. [Abstract] [Full Text] [PDF]