Department of Genetics, Collegue of Science, Kazerun branch, Islamic Azad University, Kazerun, Iran , email@example.com
Abstract: (1281 Views)
Background: hyper-methylation in CpG Island is one of the major mechanisms in gene silencing. In many cancers, different genes are experiencing CIHM (CpG island hyper methylation). P14 / ARF regulatory factor, involved in negative regulation of the cell cycle through the effect on P53 factor pathway. On the other hand, Interleukin 17 can be increased methylation by inflammatory effects. The purpose of this study was to study the P14/ARF gene promoter methylation and effect of Interleukin-17 on this methylation among breast cancer patients in the south of the country and its comparison with healthy people.
Materials and Methods: in this case–control study, peripheral blood of 40 patients with breast cancer who were referred to hospitals in Shiraz and 40 healthy women was used to DNA extraction by using salt out and K proteinase . Control subjects with a family history of cancer or autoimmune diseases were excluded from the study. We used PCR-RFLP method In order to study of Interleukin-17 gene polymorphism, and MSPCR method was used to study of P14/ARF gene promoter methylation. The results of the study were studied by using SPSS software, Arlequin, chi-square and Hardy-weinberg equilibrium test was used respectively.
Results: findings confirms that there was a significant association between P14/ARF gene promoter methylation and disease and mentioned gene promoter was less methylated in healthy subjects compared to patients (p<0.05). On the other hand, there is a significant association between GG genotype in IL17 F gene polymorphisms and P14 /ARF gene methylation (P<0.05).
Conclusion: P14/ARF gene promoter’s methylation play an important role in breast cancer. Due to the decline of P14P14/ARF gene promoters methylation and its association with this disease, seems that it could be used as a biomarker for diagnosis.
11. Vanyushin BF, Tkacheva SG, Belozersky AN. Rare bases in animal DNA. Nature 1970; 225(5236): 948-9. [PubMed] [Google Scholar]
12. Antequera F, Bird A. Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci U S A 1993; 90(24): 11995-9. [PubMed] [Google Scholar]
13. Duro D, Bernard O, Della Valle V, et al. A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies. Oncogene 1995; 11(1): 21-9. [PubMed]
14. Sharpless NE. INK4a/ARF: a multifunctional tumor suppressor locus. Mutat Res 2005; 576(1-2): 22-38. [PubMed] [Google Scholar]
15. Harland M, Taylor CF, Chambers PA, et al. A mutation hotspot at the p14ARF splice site. Oncogene 2005; 24(28): 4604-8. [PubMed] [Google Scholar]
16. Hizawa N, Kawaguchi M, Huang SK, et al. Role of interleukin-17F in chronic inflammatory and allergic lung disease. Clin Exp Allergy 2006; 36(9): 1109-14. [PubMed] [Google Scholar]
17. Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005; 6(11): 1133-41. [PubMed] [Google Scholar]
18. Yang XO, Chang SH, Park H, et al. Regulation of inflammatory responses by IL-17F. J Exp Med 2008; 205(5): 1063-75. [PubMed] [Google Scholar]
19. Fossiez F, Djossou O, Chomarat P, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996; 183(6): 2593-603. [PubMed] [Google Scholar]
20. Wu X, Zeng Z, Chen B, et al. Association between polymorphisms in interleukin-17A and interleukin-17F genes and risks of gastric cancer. Int J Cancer 2010; 127(1): 86-92. [PubMed] [Google Scholar]
21. Tahara T, Shibata T, Nakamura M, et al. Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa. Int J Mol Med 2009; 24(4): 563-9. [PubMed] [Google Scholar]
22. Herman JG, Latif F, Weng Y, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A 1994; 91(21): 9700-4. [PubMed] [Google Scholar]
23. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 1995; 55(20): 4525-30. [PubMed] [Google Scholar]
24. Herman JG, Jen J, Merlo A, et al. Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res 1996; 56(4): 722-7. [PubMed] [Google Scholar]
25. Issa JP. CpG-island methylation in aging and cancer. Curr Top Microbiol Immunol 2000; 249: 101-18. [PubMed]
26. Kawaguchi M, Adachi M, Oda N, et al. IL-17 cytokine family. J Allergy Clin Immunol 2004; 114(6): 1265-73. [PubMed] [Google Scholar]
27. Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 2007; 17(5): 435-40. [PubMed] [Google Scholar]
28. Chang SH, Dong C. IL-17F: regulation, signaling and function in inflammation. Cytokine 2009; 46(1): 7-11. [PubMed] [Google Scholar]
29. Nordang GB, Viken MK, Hollis-Moffatt JE, et al. Association analysis of the interleukin 17A gene in Caucasian rheumatoid arthritis patients from Norway and New Zealand. Rheumatology (Oxford) 2009; 48(4): 367-70. [PubMed] [Google Scholar]
30. Arisawa T, Tahara T, Shibata T, et al. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol 2008; 28(1): 44-9. [PubMed] [Google Scholar]
31. Flanagan JM, Munoz-Alegre M, Henderson S, et al. Gene-body hypermethylation of ATM in peripheral blood DNA of bilateral breast cancer patients. Hum Mol Genet 2009; 18(7): 1332-42. [PubMed] [Google Scholar]
32. Askari M, Sobti RC, Nikbakht M, et al. Promoter hypermethylation of tumour suppressor genes (p14/ARF and p16/INK4a): case-control study in North Indian population. Mol Biol Rep 2013; 40(8): 4921-8. [PubMed] [Google Scholar]
33. Schmitt CA, Fridman JS, Yang M, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002; 109(3): 335-46. [PubMed] [Google Scholar]
34. Linggi B, Muller-Tidow C, van de Locht L, et al. The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat Med 2002; 8(7): 743-50. [PubMed] [Google Scholar]
35. Wazir U, Jiang WG, Yasaei H, et al. P14ARF is down-regulated during tumour progression and predicts the clinical outcome in human breast cancer. Anticancer Res 2013; 33(5): 2185-9. [PubMed] [Google Scholar]
36. Shulenina LV, Ushenkova LN, Ledin EV, et al. Expression of P53, NPM1, Kras, c-Myc, p14(ARF) genes in blood cells of cancer patients before and after radiation therapy]. Radiats Biol Radioecol 2012; 52(6): 572-81. [PubMed]
Naeimi S. Study of P14/ARF Gene Promoter Methylation and Effect of Interleukin-17 Gene Polymorphism on this Methylation among Breast Cancer Patients. Iran South Med J. 2016; 19 (5) :809-818 URL: http://ismj.bpums.ac.ir/article-1-829-en.html