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:: Volume 28, Issue 4 (10-2020) ::
Journal of Ilam University of Medical Sciences 2020, 28(4): 66-78 Back to browse issues page
Investigation of Expression and Methylation Status of ELF5 Gene Promoter in Patients with Breast Cancer
Azar Heidarizadi1 , Mahdieh Salimi * 2, Hossein Mozdarani3
1- Dept of Genetics, Fars Science and Research Branch, Islamic Azad University, Marvdasht, Iran
2- Dept of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran , salimi@nigeb.ac.ir
3- Dept of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Abstract:   (1763 Views)
Introduction: Breast cancer is the most prevalent cancer among Iranian women. ELF5 gene as a transcription factor member of the ETS family could play a key role in breast cancer neoplasms, especially basal-like and endocrine-resistant subtypes. The changes in the gene promoter methylation pattern are considered proper targets in the therapeutic strategies. This study aimed to investigate the frequency of this epigenetic phenomenon and ELF5 gene expression as well as their association with pathologic and clinical characteristics of Iranian patients suffering from this cancer.
Materials & Methods: In order to investigate the ELF5 promoter methylation, 134 breast tissues were analyzed using methylation-specific PCR method. Moreover, 164 tumoral and 10 normal breast tissues retrieved from breast reduction surgery were assessed using Real-Time RT-PCR to analyze the gene expression.
Ethics code: 52d/4922, 6.10.2016
Findings: The data revealed that about 70% of the breast cancer tumoral specimens showed ELF5 promoter methylated pattern. Furthermore, the down-regulation of ELF5 gene expression was significantly associated with higher cancer stages, being triple-negative, and invasion.
Discussions & Conclusions: The results revealed that an increase in the ELF5 promoter methylation frequency in patients, compared to the control tissues, and its association with poor prognosis indicators may propose the ELF5 promoter methylation as a possible candidate in further studies to confirm the poor prognostic role of this biomarker in breast cancer.
Keywords: Breast neoplasms, ELF5, Epigenetics, Gene expression, Methylation
Full-Text [PDF 734 kb]   (1022 Downloads)    
Type of Study: Research | Subject: Molecular Genetics
Received: 2019/09/15 | Accepted: 2020/04/14 | Published: 2020/10/31
1. Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, Ebrahimi M. Breast cancer in Iran an epidemiological review. Breast J 2007; 13:383-91. doi.10.1111/j.1524-474
2. Dumitrescu RG. Early epigenetic markers for precision medicine. Meth Mol Biol 2018; 1856:3-17. doi.10.1007/978-1-4939-8751-1-1.
3. Ramalho J, Henrique R, Jeronimo C. Methylation specific PCR in Tost J DNA methylation protocols. Meth Mole Biol2018; 1708:123-9. doi.10.1007/978-1-4939-7481-8-23
4. Abbasi B, Ansarinejad N, Fardad F, Nasiripour S, Ramim T. [Breast cancer epigenetics]. Tehran Uni Med J 2016; 74:535-44. (Persian)
5. Brancaccio M, Natale F, Falco G, Angrisano T. Cell free DNA methylation the new frontiers of pancreatic cancer biomarkers discovery. Genes2020; 11:14. doi.10.3390/genes11010014
6. Lee HJ, Hinshelwood RA, Bouras T, Gallego D, Valdes F, Blazek K, et al. Lineage specific methylation of the Elf5 promoter in mammary epithelial cells. Stemcells 2011; 29:1611-9. doi.10.1002/stem.706
7. Zhang X, Lin J, Ma Y, Zhao J. Overexpression of E74-like factor 5 inhibits migration and invasion of ovarian cancer cells. Int J Exp Clin Res2019; 25:856. doi.10.12659/MSM.913058
8. Luk IY, Reehorst CM, Mariadason JM. ELF3 and ELF5 and EHF and SPDEF transcription factors in tissue homeostasis and cancer. Molecules 2018; 23:2191. doi.10.3390/molecules23092191
9. Zhou J, Ng AY, Tymms MJ, Jermiin LS, Seth AK, Thomas RS, et al. A novel transcription factor ELF5 belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15 a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene 1998; 17:2719-32. doi.10.1038/sj.onc.1202198
10. Omata F, Mcnamara KM, Suzuki K, Abe E, Hirakawa H, Ishida T, et al. Effect of the normal mammary differentiation regulator ELF5 upon clinical outcomes of triple negative breast cancers patients. Breast Cancer2018 1; 25:489-96. doi.10.1007/s12282-018-0842-z.
11. Lapinskas EJ, Svobodova S, Davis ID, Cebon J, Hertzog PJ, Pritchard MA. The ets transcription factor elf5 functions as a tumor suppressor in the kidney. Twin Res Hum Gene2011; 14:316-22. doi.10.1375/twin.14.4.316.
12. Metzger DE, Xu Y, Shannon JM. Elf5 is an epithelium specific fibroblast growth factor sensitive transcription factor in the embryonic lung. Dev Dynam Off Publ Am Associ Anatom2007; 236:1175-92. doi.10.1002/dvdy.21133.
13. Chakrabarti R, Hwang J, Blanco MA, Wei Y, Lukacisin M, Romano RA, et al. Elf5 inhibits the epithelial mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biol2012; 14:1212-22. doi.10.1038/ncb2607.
14. Wu B, Cao X, Liang X, Zhang X, Zhang W, Sun G, et al. Epigenetic regulation of Elf5 is associated with epithelial-mesenchymal transition in urothelial cancer. Plos One2015 28;10: 117510. doi.10.1371/journal.pone.0117510.
15. Rogers RL, Seuningen I, Gould J, Hertzog PJ, Naylor MJ, Pritchard MA. Transcript profiling of Elf5+/− mammary glands during pregnancy identifies novel targets of Elf5. Plos One 2010 7; 5: 13150. doi.10.1371/journal.pone.0013150.
16. Furth PA, Nakles RE, Millman S, Diaz ES, Cabrera MC. Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer. Breast Cancer Res Ac2011; 13:220. doi.10.1186/bcr2921.
17. Chean J, Chen CJ, Shively JE. ETS transcription factor ELF5 induces lumen formation in a 3D model of mammary morphogenesis and its expression is inhibited by Jak2 inhibitor TG101348. ExpCell Res2017; 359:62-75. doi.10.1016/j.yexcr.2017.08.008.
18. Siegel PM, Muller WJ. Transcription factor regulatory networks in mammary epithelial development and tumorigenesis. Oncogene2010; 29:2753-9. doi.10.1038/onc.2010.43.
19. Piggin CL, Roden DL, Gallego D, Lee HJ, Oakes SR, Ormandy CJ. ELF5 isoform expression is tissue specific and significantly altered in cancer. Breast Cancer Res2016; 18:4. doi.10.1186/s13058-015-0666-0.
20. Okamura Y, Aoki Y, Obayashi T, Tadaka S, Ito S, Narise T, et al. Coexpression database for animal species by DNA-microarray and RNAseq based expression data with multiple quality assessment systems. Nucle Acids Res2015; 43: 82-6. doi.10.1093/nar/gku1163.
21. Fitzgerald LM, Browne EP, Christie KD, Punska EC, Simmons LO, Williams KE, et al. ELF5 and dok7 regulation in anti-estrogen treated cells and tumors. Cancer Cell Int2016; 16:8. doi.10.1186/s12935-016-0282-9.
22. Mathsyaraja H, Ostrowski MC. Setting Snail2s pace during EMT. Nature Cell Biolo 2012; 14:123-7. doi.10.1038/ncb2616
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Ethics code: 52d/4922, 6.10.2016

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Heidarizadi A, Salimi M, Mozdarani H. Investigation of Expression and Methylation Status of ELF5 Gene Promoter in Patients with Breast Cancer. Journal of Ilam University of Medical Sciences 2020; 28 (4) :66-78
URL: http://sjimu.medilam.ac.ir/article-1-6003-en.html

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