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01.04.2014 | Research Article

Overexpression of HER-2/neu protein attenuates the oxidative systemic profile in women diagnosed with breast cancer

verfasst von: Vanessa J. Victorino, Fernanda C. Campos, Ana C. S. A. Herrera, Andréa N. Colado Simão, Alessandra L. Cecchini, Carolina Panis, Rubens Cecchini

Erschienen in: Tumor Biology | Ausgabe 4/2014

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Abstract

About 20 % of breast cancer patients over-express the human epidermal growth factor receptor-2 (HER2), which is associated with enhanced tumor malignancy. The influence of HER2 overexpression on oxidant/antioxidant parameters in humans remains unknown; therefore, we investigated the oxidative profile in women according to their HER2 status. Fifty-two controls and 52 breast cancer (BC) patients were enrolled. The BC patients were subdivided into HER−, negative for HER2 overexpression, and HER+, positive for HER2 overexpression. Oxidative stress profilling was measured by malondialdehyde (MDA), free 8-isoprostane F2, protein carbonyl content, nitric oxide (NO), total radical antioxidant parameter (TRAP), superoxide dismutase (SOD), catalase activity, and glutathione (GSH) levels. Total thiol content and lipoperoxidation were evaluated in HCC1954 and MCF-7. Cells overexpressing HER2 presented enhanced oxidative stress. Increased erythrocyte lipoperoxidation was found in BC patients, while plasma lipoperoxidation was detected in both the BC and HER− groups. Decreased MDA levels were found in the HER+ group, suggesting that HER2 overexpression may protects against plasma lipoperoxidation. No alteration was found for 8-isoprostane F2, NO, and carbonyl content. TRAP was decreased in BC patients, while HER2 overexpression increased SOD and prevented decreased GSH levels. These data help to understand the HER2 overexpression in oxidative signaling and may enable the development of new strategies for anti-HER2 therapy.

World Health Organization (WHO) 2011 <http://www.who.int/topics/cancer/en>

Gutierrez C, Schiff R. HER2 biology, detection, and clinical implications. Arch Pathol Lab Med. 2011;135:55–62.PubMedCentralPubMed

Yarden Y, Sliwkowski MX. Untangling the Erbb signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.PubMedCrossRef

Aranda V, Haire T, Nolan ME, et al. MuthuswamyPar6–aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat Cell Biol. 2006;8:1235–45.PubMedCrossRef

Kim AH, Khursigara G, Sun X, Franke TF, Chao MV. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase. Mol Cell Biol. 2001;21:893–901.PubMedCentralPubMedCrossRef

Tang ED, Nunez G, Barri FG, Guan KL. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem. 1999;274:16741–6.PubMedCrossRef

Dittmar T, Husemann A, Schewe Y, Nofer J, Niggemann B, Zänker KS, Brandt BH. Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR1. FASEB J. 2002; 1823–25.

Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu overexpressing cells. Nat Cell Biol. 2001;3:245–52.PubMedCrossRef

Dan HC, Sun M, Yang L, et al. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem. 2002;277:35364–70.PubMedCrossRef

10.

Higashiyama M, Doi O, Kodama K, et al. MDM2 gene amplification and expression in non small cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Brit J Cancer. 1997;9:1302–8.CrossRef

11.

Azambuja E, Bedard PL, Suter T, Piccart-Gebhart M. Cardiac toxicity with anti-HER-2 therapies-what have we learned so far? Targ Oncol. 2009;4:77–88.CrossRef

12.

Aird KM, Allensworth JL, Batinic-Haberle I, Lyerly HK, Dewhirst MW, Devi GR. ErbB1/2 tyrosine kinase inhibitor mediates oxidative stress-induced apoptosis in inflammatory breast cancer cells. Breast Cancer Res Treat. 2012;132(1):109–19.PubMedCentralPubMedCrossRef

13.

Dogan I, Cumaoglu A, Aricioglu A, Ekmekci A. Inhibition of ErbB2 by Herceptin reduces viability and survival, induces apoptosis and oxidative stress in Calu-3 cell line. Mol Cell Biochem. 2011;347:41–51.PubMedCrossRef

14.

Timolati F, Ott D, Pentassuglia L, Giraud MN, Perriard JC, Suter TM, et al. Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation–contraction coupling and reduces oxidative stress in adult rat cardiomyocytes. J Mol Cell Cardiol. 2006;41:845–54.PubMedCrossRef

15.

Gordon LI, Burke MA, Singh AT, Prachand S, Lieberman ED, Sun L, et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J Biol Chem. 2009;284(4):2080–7.PubMedCentralPubMedCrossRef

16.

Zeglinski M, Ludke A, Jassal DS, Singal PK. Trastuzumab-induced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol. 2011;16(3):70–4.PubMedCentralPubMed

17.

Forman HJ, Fukuto JM, Miller T, Zhang H, Rinna A, Levy S. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys. 2008;2:183–95.CrossRef

18.

Angeloni C, Motori E, Fabbri D, Malaguti M, Leoncini E, Lorenzini A, et al. H2O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation. Am J Physiol. 2011;300(6):H2196–205. doi:10.1152/ajpheart.00934.2010.

19.

Chang CY, Chan HL, Lin HY, Way TD, Kao MC, Song MZ, et al. Rhein induces apoptosis in human breast cancer cells. Evid Based Complement Alternat Med. 2011;2012:952504.PubMedCentralPubMed

20.

Kuo HP, Chuang TC, Yeh MH, et al. Growth suppression of HER2-overexpressing breast cancer cells by berberine via modulation of the HER2/PI3K/Akt signaling pathway. J Agric Food Chem. 2011;59(15):8216–24.PubMedCrossRef

21.

Seo HS, Choi HS, Choi HS, et al. Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factor-{kappa}B signaling in HER2-overexpressing breast cancer cells. Anticancer Res. 2011;31(10):3301–13.PubMed

22.

Shin-Kang S, Ramsauer VP, Lightner J et al. Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. Free Radic Biol Med. 2011;15;51(6):1164–74.

23.

Halliwell B. Oxidative stress and cancer: have we moved forward? Biochem J. 2007;401:1–11.PubMedCrossRef

24.

Cadenas C, Franckenstein D, Schmidt M, Gehrmann M, Hermes M, Geppert B, et al. Research aortic thioredoxin reductase 1 and thioredoxin interacting protein in prognosis of breast cancer. Breast Cancer Res. 2010;12:R44.PubMedCentralPubMedCrossRef

25.

Perquin M, Oster T, Maul A, Froment N, Untereiner M, Bagrel D. The glutathione-related detoxification system is increased in human breast cancer in correlation with clinical and histopathological features. J Cancer Res Clin Oncol. 2001;127:368–74.PubMedCrossRef

26.

Tsai SM, Hou MF, Wu SH, Hu BW, Yang SF, Chen WT, et al. Expression of manganese superoxide dismutase in patients with breast cancer. Kaohsiung J Med Sci. 2011;27:167–72.PubMedCrossRef

27.

Chuang TC, Liu JY, Lin CT, Tang YT, Yeh MH, Chang SC, et al. Human manganese superoxide dismutase suppresses HER2/neu-mediated breast cancer malignancy. FEBS Lett. 2007;581:4443–9.PubMedCrossRef

28.

Hyne NE, Lane HA. Erbb receptors and cancer: the complexity of targeted inhibitors. Nat Rev. 2005;5:341–54.CrossRef

29.

Panis C, Pizzatti L, Herrera ACSA, Cecchini R, Abdelhay E. Putative circulating markers of the early and advanced stages of breast cancer identified by high-resolution label-free proteomics. Cancer Lett. 2013;330:57–66.PubMedCrossRef

30.

Bradford MM. Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.PubMedCrossRef

31.

Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192–205.PubMedCrossRef

32.

Herrera ACSA, Panis C, Victorino VJ et al. Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients. Cancer Immunol Immunother. 2012; doi:10.1007/s00262-012-1283-8.

33.

Victorino VJ, Panis C, Campos FC et al. Decreased oxidant profile and increased antioxidant capacity in naturally postmenopausal women. AGE 2012. doi:10.1007/s11357-012-9431-9.

34.

Panis C, Lemos LGT, Victorino VJ et al. Immunological effects of Taxol and Adryamicin in breast cancer patients. Cancer Immunol Immunother 2012; doi:10.1007/s00262-011-1117-0.

35.

Panis C, Mazzuco TL, Costa CZF, Victorino VJ, Tatakihara VLH, Yamauchi LM, et al. Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice. Exp Parasitol. 2011;127:58–65.PubMedCrossRef

36.

Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994;233:357–63.PubMedCrossRef

37.

Repetto M, Reides C, Carretero MLG, Costa M, Griemberg G, Llesuy S. Oxidative stress in blood of HIV infected patients. Clin Chim Acta. 1996;225:107–17.CrossRef

38.

Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:474–96.CrossRef

39.

Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.PubMedCrossRef

40.

Panis C, Victorino VJ, Herreira ACSA et al. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer. Breast Cancer Res Tr. 2011; doi:10.1007/s10549-011-1851-1.

41.

Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. In: oxygen is a toxic gas – an introduction to oxygen toxicity and reactive species. 4th edn. New York: Oxford University 2007; pp 1–28.

42.

Jian J, Yang Q, Dai J, Eckard J, Axelrod D, Smith J, et al. Effects of iron deficiency and iron overload on angiogenesis and oxidative stress—a potential dual role for iron in breast cancer. Free Rad Biol Med. 2011;50:841–7.PubMedCentralPubMedCrossRef

43.

Zwart LL, Meerman JHN, Commandeur JNM, Vermeulen NP. Biomarkers of free radical damage applications in experimental animals and in humans. Free Rad Biol Med. 1999;26:202–26.PubMedCrossRef

44.

Colado-Simão AN, Suzukawa AA, Casado MF, Oliveira RD, Cecchini R. Genistein abrogates pre-hemolytic and oxidative stress damage induced by 2,2′-azobis (Amidinopropane). Life Sci. 2006;11:1202–10.CrossRef

45.

Badid N, Ahmed FZB, Merzouk H, Belbraouet S, Mokhtari N, Merzouk SA, et al. Oxidant/antioxidant status, lipids and hormonal profile in overweight women with breast cancer. Pathol Oncol Res. 2010;16:159–67.PubMedCrossRef

46.

Karihtala P, Kauppila S, Puistola U, Jukkola-Vuorinen A. Divergent behaviour of oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) in breast carcinogenesis. Histopathology. 2011;58:854–62.PubMedCrossRef

47.

Gago-Dominguez M, Jiang X, Castelao JE. Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis. Breast Cancer Res. 2007;9:201.PubMedCentralPubMedCrossRef

48.

Panis C, Herreira ACSA, Victorino VJ et al. Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy. Breast Cancer Res Tr. 2011; doi:10.1007/s10549-011-1693-x.

49.

Henson ES, Johnston JB, Los M, Gibson SB. Clinical activities of the epidermal growth factor receptor family inhibitors in breast cancer. Biologics: Targets Ther. 2007;1(3):229–39.

50.

Dong-Yun S, Yu-Ru D, Shan-Lin L, Ya-Dong Z, Lian W. Redox stress regulates cell proliferation and apoptosis of human hepatoma through Akt protein phosphorylation. FEBS Lett. 2003;542(1–3):60–4.PubMedCrossRef

51.

Akca H, Demiray A, Aslan M, Acikbas I, Tokgun O. Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKTpathway in non-small cell lung cancer cell lines. J Enzyme Inhib Med Chem. 2013;28(3):539–44.PubMedCrossRef

52.

Dal-Cim T, Molz S, Egea J, Parada E, Romero A, Budni J, et al. Guanosine protects human neuroblastoma SH-SY5Y cells against mitochondrial oxidative stress by inducing heme oxigenase-1 via PI3K/Akt/GSK-3b pathway. Neurochem Int. 2012;61:397–404.PubMedCrossRef

53.

Aruoma OI. Free radicals, oxidative stress, and antioxidants in human health and disease. JAOCS. 1998;75:199–212.

54.

Zou X, Zhihui F, Li Y et al. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. J Nutr Biochem 2011; doi:10.1016/j.jnutbio.2011.05.006.

Titel: Overexpression of HER-2/neu protein attenuates the oxidative systemic profile in women diagnosed with breast cancer
verfasst von: Vanessa J. Victorino
Fernanda C. Campos
Ana C. S. A. Herrera
Andréa N. Colado Simão
Alessandra L. Cecchini
Carolina Panis
Rubens Cecchini
Publikationsdatum: 01.04.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 4/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1391-x

Springer Medizin

Overexpression of HER-2/neu protein attenuates the oxidative systemic profile in women diagnosed with breast cancer

Abstract

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