Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

BackgroundPeroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI) in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1) as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1.MethodsWe investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR) and Western blot.ResultsLevels of messenger RNA (mRNA) for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid). Among members of the Prx family (Prx I-VI) and Trx family (Trx1, Trx2), Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue.ConclusionPrx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

[1]  D. Noh,et al.  Overexpression of peroxiredoxin in human breast cancer. , 2001, Anticancer research.

[2]  T. Sakai,et al.  Thioredoxin-dependent Redox Regulation of p53-mediated p21 Activation* , 1999, The Journal of Biological Chemistry.

[3]  S. Rhee,et al.  Identification of a New Type of Mammalian Peroxiredoxin That Forms an Intramolecular Disulfide as a Reaction Intermediate* , 2000, The Journal of Biological Chemistry.

[4]  Sang Won Kang,et al.  Peroxiredoxins in breast carcinoma. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  J. McManaman,et al.  Alcohol-induced breast cancer: a proposed mechanism. , 1999, Free radical biology & medicine.

[6]  Y. Makino,et al.  Functional modulation of estrogen receptor by redox state with reference to thioredoxin as a mediator. , 1997, Nucleic acids research.

[7]  V. Ferrans,et al.  Requirement for Generation of H2O2 for Platelet-Derived Growth Factor Signal Transduction , 1995, Science.

[8]  Y. Yamaoka,et al.  Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide. , 1994, Immunology letters.

[9]  T. Finkel Oxygen radicals and signaling. , 1998, Current opinion in cell biology.

[10]  J. Yodoi,et al.  Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin. , 1992, Biochemical and biophysical research communications.

[11]  H. Masutani,et al.  Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the rat retina. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[12]  P. Karplus,et al.  Dimers to doughnuts: redox-sensitive oligomerization of 2-cysteine peroxiredoxins. , 2002, Biochemistry.

[13]  H. Masutani,et al.  Expression and growth‐promoting effect of adult t‐cell leukemia‐derived factor a human thioredoxin homologue in hepatocellular carcinoma , 1992, Cancer.

[14]  H. Nakamura,et al.  Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus. , 1995, Human reproduction.

[15]  N. Cairns,et al.  Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down syndrome. , 2001, Journal of neural transmission. Supplementum.

[16]  K. Umesono,et al.  Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system. , 1996, The Journal of clinical investigation.

[17]  K. Schulze-Osthoff,et al.  Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-kappa B and AP-1. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. van Dorsselaer,et al.  A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized in vivo at the active-site cysteine during oxidative stress. , 2002, The Biochemical journal.

[19]  H. Yoshida,et al.  Peroxiredoxin I expression in human thyroid tumors. , 1999, Cancer letters.

[20]  S. Rhee,et al.  Mammalian Peroxiredoxin Isoforms Can Reduce Hydrogen Peroxide Generated in Response to Growth Factors and Tumor Necrosis Factor-α* , 1998, The Journal of Biological Chemistry.

[21]  Woojin Jeong,et al.  Regulation of Peroxiredoxin I Activity by Cdc2-mediated Phosphorylation* , 2002, The Journal of Biological Chemistry.

[22]  Y. Yamaoka,et al.  Inverse correlation of thioredoxin expression with estrogen receptor- and p53-dependent tumor growth in breast cancer tissues. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  R. Nelson,et al.  Dietary iron and colorectal cancer risk. , 1992, Free radical biology & medicine.

[24]  K. Schulze-Osthoff,et al.  転写因子NF‐κBとAP‐1の活性化に及ぼすチオレドキシンと抗酸化剤の異なった効果 , 1994 .

[25]  H. Masutani,et al.  Coexpression of adult T‐cell leukemia‐derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium , 1991, Cancer.

[26]  A. Iwamatsu,et al.  Variants of peroxiredoxins expression in response to hydroperoxide stress. , 2001, Free radical biology & medicine.

[27]  S. Rhee,et al.  Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. , 2005, Free radical biology & medicine.

[28]  H. Masutani,et al.  Molecular interaction during pregnancy: Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus , 1995 .

[29]  C. Ambrosone Oxidants and antioxidants in breast cancer. , 2000, Antioxidants & redox signaling.

[30]  N. Dhalla,et al.  Role of oxidative stress in cardiovascular diseases , 2000, Journal of hypertension.

[31]  K. Kolaja,et al.  The role of oxidative stress in chemical carcinogenesis. , 1998, Environmental health perspectives.

[32]  Y. Yamaoka,et al.  Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer. , 2000, Cancer detection and prevention.

[33]  G. Church,et al.  Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[34]  H. Harada,et al.  Peroxiredoxin I expression in oral cancer: a potential new tumor marker. , 2000, Cancer letters.

[35]  M. Yüksel,et al.  Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. , 2001, Cancer letters.

[36]  J. Yodoi,et al.  Redox control of resistance to cis-diamminedichloroplatinum (II) (CDDP): protective effect of human thioredoxin against CDDP-induced cytotoxicity. , 1996, The Journal of clinical investigation.