ESR1 and GPX1 genes expression level in human malignant and non-malignant breast tissues

  • Magdalena Beata Król Department of Biological and Environmental Monitoring, Nofer Institute of Occupational Medicine, Łódź, Poland http://orcid.org/0000-0001-7856-2968
  • Michał Galicki Department of Surgical Oncology, Copernicus Memorial Hospital, Cancer Center, Łódź, Poland
  • Peter Grešner Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland
  • Edyta Wieczorek Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland
  • Ewa Jabłońska Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland
  • Edyta Reszka Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland
  • Zbigniew Morawiec Department of Surgical Oncology, Copernicus Memorial Hospital, Cancer Center, Łódź, Poland
  • Wojciech Wąsowicz Department of Biological and Environmental Monitoring, Nofer Institute of Occupational Medicine, Łódź, Poland
  • Jolanta Gromadzińska Department of Biological and Environmental Monitoring, Nofer Institute of Occupational Medicine, Łódź, Poland

Abstract

Background: The aim of this study was to find out whether the mRNA expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in tumor and adjacent tumor-free breast tissue and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor.

Methods: We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients.

Results: ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue compared to the non-malignant one. Down-regulation of these gene were independent of tumor histopathology classification and clinicopathological factors while ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively).

Conclusion: These data suggest that down-regulation of ESR1 and GPX1 are independent on clinicopathological factors. Down-regulation of ESR1 gene expression enhanced with the development of the disease. Moreover, GPX1 and ESR1 genes expression are interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

Author Biography

Magdalena Beata Król, Department of Biological and Environmental Monitoring, Nofer Institute of Occupational Medicine, Łódź, Poland

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (resolution no. 01/2011) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

Amir E, Clemons M, Purdie CA, Miller N, Quinlan P, Geddie W, Coleman RE, Freedman OC, Jordan LB, Thompson AM (2012) Tissue Confirmation of Disease Recurrence in Breast Cancer Patients: Pooled Analysis of Multi-Centre, Multi-Disciplinary Prospective Studies. Cancer Treat Rev 38: 708–714. http://dx.doi.org/10.1016/j.ctrv.2011.11.006.

Arnér ESJ, Holmgren A (2000) Physiological Functions of Thioredoxin and Thioredoxin Reductase. Eur J Biochem 267: 6102–6109. http://dx.doi.org/10.1046/j.1432-1327.2000.01701.x.

Au WW, Abdou-Salama S, Al-Hendy A (2007) Inhibition of Growth of Cervical Cancer Cells Using a Dominant Negative Estrogen Receptor Gene. Gynecol Oncol 104: 276–80. http://dx.doi.org/10.1016/j.ygyno.2006.10.015.

Barrera G (2012) Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy. ISRN Oncol 2012: 1–21. http://dx.doi.org/10.5402/2012/137289.

Behrens D, Gill JH, Fichtner I (2007) Loss of Tumourigenicity of Stably ERbeta-Transfected MCF-7 Breast Cancer Cells. Mol Cell Endocrinol 274: 19–29. http://dx.doi.org/10.1016/j.mce.2007.05.012.

Bojar I, Cvejić R, Glowacka MD, Koprowicz A, Humeniuk E, Owoc A (2012) Morbidity and Mortality due to Cervical Cancer in Poland after Introduction of the Act - National Programme for Control of Cancerous Diseases. Ann Agric Environ Med 19: 680–685.

Casares C, Ramirez-Camacho R, Trinidad A, Roldan A, Jorge E, Garcia-Berrocal JR (2012) Reactive Oxygen Species in Apoptosis Induced by Cisplatin: Review of Physiopathological Mechanisms in Animal Models. Eur Arch Oto-Rhino-Laryngology 269: 2455–2459. http://dx.doi.org/10.1007/s00405-012-2029-0.

Chiu WH, Luo SJ, Chen CL, Cheng JH, Hsieh CY, Wang CY, Huang WC, Su WC, Lin CF (2012) Vinca Alkaloids Cause Aberrant ROS-Mediated JNK Activation, Mcl-1 Downregulation, DNA Damage, Mitochondrial Dysfunction, and Apoptosis in Lung Adenocarcinoma Cells. Biochem Pharmacol 83: 1159–1171. http://dx.doi.org/10.1016/j.bcp.2012.01.016.

Huang B, Omoto Y, Iwase H, Yamashita H, Toyama T, Coombes RC, Filipovic A, Warner M, Gustafsson J-Å (2014) Differential Expression of Estrogen Receptor Α, β1, and β2 in Lobular and Ductal Breast Cancer. Proc Natl Acad Sci U S A 111: 1933–8. http://dx.doi.org/10.1073/pnas.1323719111.

Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (1990) Two Distinct Estrogen-Regulated Promoters Generate Transcripts Encoding the Two Functionally Different Human Progesterone Receptor Forms A and B. EMBO J 9: 1603–14.

Kim KK, Lange TS, Singh RK, Brard L, Moore RG (2012) Tetrathiomolybdate Sensitizes Ovarian Cancer Cells to Anticancer Drugs Doxorubicin, Fenretinide, 5-Fluorouracil and Mitomycin C. BMC Cancer 12: 147. http://dx.doi.org/10.1186/1471-2407-12-147.

Klinge CM (2001) Estrogen Receptor Interaction with Estrogen Response Elements. Nucleic Acids Res 29: 2905–2919. http://dx.doi.org/10.1093/nar/29.14.2905.

Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S (2002) Tissue Lipid Peroxidation and Antioxidant Status in Patients with Adenocarcinoma of the Breast. Clin Chim Acta 325: 165–170.

Kushner PJ, Agard DA, Greene GL, Scanlan TS, Shiau AK, Uht RM, Webb P (2000) Estrogen Receptor Pathways to AP-1. J Steroid Biochem Mol Biol 74: 311–7.

Liang X, Lu B, Scott GK, Chang CH, a Baldwin M, Benz C (1998) Oxidant Stress Impaired DNA-Binding of Estrogen Receptor from Human Breast Cancer. Mol Cell Endocrinol 146: 151–161.

Lin Z, Reierstad S, Huang C-C, Bulun SE (2007) Novel Estrogen Receptor-Alpha Binding Sites and Estradiol Target Genes Identified by Chromatin Immunoprecipitation Cloning in Breast Cancer. Cancer Res 67: 5017–24. http://dx.doi.org/10.1158/0008-5472.CAN-06-3696.

Lubos E, Loscalzo J, Handy DE (2011) Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid Redox Signal 15: 1957–1997. http://dx.doi.org/10.1089/ars.2010.3586.

Min S, Kim H, Jung E (2012) Prognostic Significance of Glutathione Peroxidase 1 (GPX1) down-Regulation and Correlation with Aberrant Promoter Methylation in Human Gastric Cancer. Anticancer Res 32: 3169–3176.

Mustacich D, Powis G (2000) Thioredoxin Reductase. Biochem J 346: 1–8.

Nalkiran I, Turan S, Arikan S, Kahraman ÖT, Acar L, Yaylim I, Ergen A (2015) Determination of Gene Expression and Serum Levels of MnSOD and GPX1 in Colorectal Cancer. Anticancer Res 35: 255–9.

Paruthiyil S, Parmar H, Kerekatte V, Cunha GR, Firestone GL, Leitman DC (2004) Estrogen Receptor Beta Inhibits Human Breast Cancer Cell Proliferation and Tumor Formation by Causing a G2 Cell Cycle Arrest. Cancer Res 64: 423–8.

Pfaffl MW, Horgan GW, Dempfle L (2002) Relative Expression Software Tool (REST) for Group-Wise Comparison and Statistical Analysis of Relative Expression Results in Real-Time PCR. Nucleic Acids Res 30: e36.

Portakal O, Ozkaya O, Inal ME, Bozan B, Kosan M, Sayek I (2000) Coenzyme Q10 Concentrations and Antoxidant Status in Tissues of Breast Cancer Patients. Clin Biochem 33: 279–284.

Punnonen K, Ahotupa M, Asaishi K, Hyiity M, Kudo R, Punnonen R (1994) Antioxidant Enzyme Activities and Oxidative Stress in Human Breast Cancer. J Cancer Res Clin Oncol 120: 374–7.

Qiu J, Xue X, Hu C, Xu H, Kou D, Li R, Li M (2016) Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. J Cancer 7: 167–173. http://dx.doi.org/10.7150/jca.10944.

Rao AK, Ziegler YS, McLeod IX, Yates JR, Nardulli AM (2008) Effects of Cu/Zn Superoxide Dismutase on Estrogen Responsiveness and Oxidative Stress in Human Breast Cancer Cells. Mol Endocrinol 22: 1113–24. http://dx.doi.org/10.1210/me.2007-0381.

Rao AK, Ziegler YS, McLeod IX, Yates JR, Nardulli AM (2009) Thioredoxin and Thioredoxin Reductase Influence Estrogen Receptor Alpha-Mediated Gene Expression in Human Breast Cancer Cells. J Mol Endocrinol 43: 251–261. http://dx.doi.org/10.1677/JME-09-0053.

Schafer FQ, Buettner GR (2001) Redox Environment of the Cell as Viewed through the Redox State of the Glutathione Disulfide/glutathione Couple. Free Radic Biol Med 30: 1191–212.

Schultz-Norton JR, Ziegler YS, Likhite VS, Yates JR, Nardulli AM (2008) Isolation of Novel Coregulatory Protein Networks Associated with DNA-Bound Estrogen Receptor Alpha. BMC Mol Biol 9: 97. http://dx.doi.org/10.1186/1471-2199-9-97.

Schwabe JW, Chapman L, Finch JT, Rhodes D (1993) The Crystal Structure of the Estrogen Receptor DNA-Binding Domain Bound to DNA: How Receptors Discriminate between Their Response Elements. Cell 75: 567–78.

Stierer M, Rosen H, Weber R, Hanak H, Spona J, Tüchler H (1993) Immunohistochemical and Biochemical Measurement of Estrogen and Progesterone Receptors in Primary Breast Cancer. Ann Surg 218: 13–21.

Ström A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson J-A (2004) Estrogen Receptor Beta Inhibits 17beta-Estradiol-Stimulated Proliferation of the Breast Cancer Cell Line T47D. Proc Natl Acad Sci U S A 101: 1566–71. http://dx.doi.org/10.1073/pnas.0308319100.

Tamir S, Izrael S, Vaya J (2002) The Effect of Oxidative Stress on ERalpha and ERbeta Expression. J Steroid Biochem Mol Biol 81: 327–332. http://dx.doi.org/10.1016/S0960-0760(02)00115-2.

Tas F, Hansel H, Belce A, Ilvan S, Argon A, Camlica H, Topuz E (2005) Oxidative Stress in Breast Cancer. Med Oncol 22: 11–5. http://dx.doi.org/10.1385/MO:22:1:011.

Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J (2007) Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. Int J Biochem Cell Biol 39: 44–84. http://dx.doi.org/10.1016/j.biocel.2006.07.001.

Webster KA, Prentice H, Bishopric NH (2001) Oxidation of Zinc Finger Transcription Factors: Physiological Consequences. Antioxid Redox Signal 3: 535–48. http://dx.doi.org/10.1089/15230860152542916.

Published
2018-05-27
Section
Articles