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DNA Methylation of RUNX3 in Papillary Thyroid Cancer

  • Ko, Hee Ja (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kim, Bo Yeon (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Jung, Chan Hee (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Chun, Sung Wan (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Mok, Ji Oh (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kim, Yeo Joo (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Park, Hyeong Kyu (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kim, Chul Hee (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kim, Sang Jin (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Byun, Dong Won (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Suh, Kyo Il (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Yoo, Myung Hi (Department of Internal Medicine, Soonchunhyang University College of Medicine) ;
  • Kang, Sung Gu (Department of Internal Medicine, Soonchunhyang University College of Medicine)
  • Published : 2012.12.01

Abstract

Background/Aims: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. Methods: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). Results: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. Conclusions: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

Keywords

References

  1. Coffman JA. Runx transcription factors and the developmental balance between cell proliferation and differentiation. Cell Biol Int 2003;27:315-324. https://doi.org/10.1016/S1065-6995(03)00018-0
  2. Blyth K, Cameron ER, Neil JC. The RUNX genes: gain or loss of function in cancer. Nat Rev Cancer 2005;5:376-387. https://doi.org/10.1038/nrc1607
  3. Bae SC, Ogawa E, Maruyama M, et al. PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. Mol Cell Biol 1994;14:3242-3252. https://doi.org/10.1128/MCB.14.5.3242
  4. Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y. AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 1994;23:425-432. https://doi.org/10.1006/geno.1994.1519
  5. Avraham KB, Levanon D, Negreanu V, et al. Mapping of the mouse homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4. Genomics 1995;25:603-605. https://doi.org/10.1016/0888-7543(95)80073-U
  6. Li QL, Ito K, Sakakura C, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002;109:113-124. https://doi.org/10.1016/S0092-8674(02)00690-6
  7. Oshimo Y, Oue N, Mitani Y, et al. Frequent loss of RUNX3 expression by promoter hypermethylation in gastric carcinoma. Pathobiology 2004;71:137-143. https://doi.org/10.1159/000076468
  8. Goel A, Arnold CN, Tassone P, et al. Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers. Int J Cancer 2004;112:754-759. https://doi.org/10.1002/ijc.20472
  9. Araki K, Osaki M, Nagahama Y, et al. Expression of RUNX3 protein in human lung adenocarcinoma: implications for tumor progression and prognosis. Cancer Sci 2005;96:227-231. https://doi.org/10.1111/j.1349-7006.2005.00033.x
  10. Li QL, Kim HR, Kim WJ, et al. Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer. Biochem Biophys Res Commun 2004;314:223-228. https://doi.org/10.1016/j.bbrc.2003.12.079
  11. Li J, Kleeff J, Guweidhi A, et al. RUNX3 expression in primary and metastatic pancreatic cancer. J Clin Pathol 2004;57:294-299. https://doi.org/10.1136/jcp.2003.013011
  12. Al-Sukhun S, Hussain M. Molecular biology of transitional cell carcinoma. Crit Rev Oncol Hematol 2003;47:181-193. https://doi.org/10.1016/S1040-8428(03)00081-7
  13. Orntoft TF, Wolf H. Molecular alterations in bladder cancer. Urol Res 1998;26:223-233. https://doi.org/10.1007/s002400050050
  14. Hwang KT, Han W, Bae JY, et al. Downregulation of the RUNX3 gene by promoter hypermethylation and hemizygous deletion in breast cancer. J Korean Med Sci 2007;22 Suppl:S24-S31.
  15. Xiao WH, Liu WW. Hemizygous deletion and hypermethylation of RUNX3 gene in hepatocellular carcinoma. World J Gastroenterol 2004;10:376-380. https://doi.org/10.3748/wjg.v10.i3.376
  16. Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 2002;21:5427-5440. https://doi.org/10.1038/sj.onc.1205600
  17. Guo WH, Weng LQ, Ito K, et al. Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor. Oncogene 2002;21:8351-8355. https://doi.org/10.1038/sj.onc.1206037
  18. Cohen MM Jr. TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A 2003;116A:1-10. https://doi.org/10.1002/ajmg.a.10750
  19. Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81:323-330. https://doi.org/10.1016/0092-8674(95)90385-2
  20. Sherr CJ. Cancer cell cycles. Science 1996;274:1672-1677. https://doi.org/10.1126/science.274.5293.1672

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