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Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues

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Abstract

Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

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Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, Korea

    H.J. Kim

  2. Department of Biology, Chonnam National University, Korea

    H.-Z. Chae

  3. Division of Chemistry and Biology, University of Incheon, Korea

    Y.-J. Kim, E.-M. Park & Y.-M. Park

  4. Genomic Research Center for Lung and Breast/Ovarian Cancer, Korea University Medical School, Korea

    Y.H. Kim

  5. Department of Pathology, Inha University College of Medicine, Korea

    T.-S. Hwang

  6. Department of Cellular Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

    Y.-M. Park

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Kim, H., Chae, HZ., Kim, YJ. et al. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues. Cell Biol Toxicol 19, 285–298 (2003). https://doi.org/10.1023/B:CBTO.0000004952.07979.3d

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