Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
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DNA METHYLATION OF TPEF GENE IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

두경부암 세포주에서 TPEF 유전자의 methylation 변이

  • Chun, So-Young (Dept. of Oral Microbiology, School of Dentistry, Kyungpook National University) ;
  • Kim, Jung-Ock (Dept. of Pathology, School of Medicine, Kyungpook National University) ;
  • Hong, Su-Hyung (Dept. of Oral Microbiology, School of Dentistry, Kyungpook National University) ;
  • Chung, Yu-Kyung (Dept. of Oral Microbiology, School of Dentistry, Kyungpook National University) ;
  • Jang, Hyun-Jung (Dept. of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University) ;
  • Shon, Yoon-Kyung (Dept. of Pathology, School of Medicine, Kyungpook National University) ;
  • Kim, Jung-Wan (Dept. of Oral Microbiology, School of Dentistry, Kyungpook National University)
  • 전소영 (경북대학교 치과대학 구강미생물학교실) ;
  • 김정옥 (경북대학교 의과대학 병리학교실) ;
  • 홍수형 (경북대학교 치과대학 구강미생물학교실) ;
  • 정유경 (경북대학교 치과대학 구강미생물학교실) ;
  • 장현중 (경북대학교 치과대학 구강악안면외과학교실) ;
  • 손윤경 (경북대학교 의과대학 병리학교실) ;
  • 김정완 (경북대학교 치과대학 구강미생물학교실)
  • Published : 2005.12.31
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Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. The molecular mechanisms involved in the development and progression of these carcinomas are not well known. Abnormalities of genomic methylation patterns have been attributed a role in carcinogenesis and local de novo methylation at tumor suppressor loci was held to be involved in silencing of tumor suppressor genes. Using Ms APPCR, we previously isolated a hypermethylated fragment corresponded to the 5' end of TPEF gene from primary liver and lung cancer cells. To confirm the inactivation of TPEF gene by hypermethylation in HNSCC, we investigated correlation between methylation pattern and expression of TPEF in 10 HNSCC cell lines. In methylation analysis such as combined-bisulfite restriction analysis(COBRA) and bisulfite sequencing, only RPMI 2650 showed none methylated pattern and another 9 cell lines showed dense methylation. The TPEF gene expression level analysis using RT-PCR showed that these 9 cell lines had not or significantly low expression levels of TPEF as compared with RPMI 2650. In addition, the increase of TPEF reexpression by 5-AzaC as demethylating agent in 9 cell lines also indicated that TPEF expression was regulated by hypermethylation. These results of this study demonstrate that epigenetic silencing of TPEF gene by aberrant methylation could play an important role in HNSCC carcinogenesis.

Keywords

References

  1. Nagler RM: Molecular aspects of oral cancer. Anticancer Res 2002;2:2977-2980
  2. Voravud N, Shin DM, Ro JY, Lee JS, Hong WK, Hittelman WN:Increased olysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res 1993;53:2874-2883
  3. Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development. Science 2001;293:1089-1093 https://doi.org/10.1126/science.1063443
  4. Baylin SB, Herman JG, Graff JR: Alterations in DNA methylation-A fundamental aspect of neoplasia. Adv Cancer Res 1998;72:141-196
  5. Singer-Sam J, Riggs AD: X chromosome inactivation and DNA methylation. EXS 1993;64:358-384
  6. Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N: The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature;1991;349:84-87 https://doi.org/10.1038/349084a0
  7. Baylin SB, Makos M, Wu JJ, Yen RW, de Bustros A, Vertino P, Nelkin BD: Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 1991;3:383-390
  8. Hansen RS, Gartler SM, Scott RC, Chen SH, Laird CD: Methylation analysis of CGG sites in the CpG islans of the human FMR1 gene. Hum Mol Genet 1992;8:571-578
  9. Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM: The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci USA 1999;96:14412-14417
  10. Issa J-P J, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB: Methylation of the estrogen receptor CpG island links aging and neoplasia in human colon. Nat Genet 1994;7:536-540 https://doi.org/10.1038/ng0894-536
  11. Ottaviano YL, Issa JP, Parl FF, Smith HS, Baylin SB, Davidson NE: Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res 1994;54:2552-2555
  12. Lee WH, Morton RA, Epstein JI: Cytidine methylation of regulatory sequences near the pi-class glutathione-S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci USA 1994;91:11733-11737
  13. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A 1994;91:9700-9704
  14. Sakai T, Toguchida J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP:Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet 1991;48:880-888
  15. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 1998;95:6870-6875
  16. Kanai Y, Hui AM, Sun L, Ushijima S, Sakamoto M, Tsuda H, Hirohashi S: DNA hypermethylation at the D17S5 locus and reduced HIC-1 mRNA expression are associated with hepatocarcinogenesis. Hepatology 1999;29:703-709 https://doi.org/10.1002/hep.510290338
  17. Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP: Davidson NE, Sidransky D, Baylin SB. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 1995;55:4525-4530
  18. Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S: Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA 1995;92:7416-7419
  19. Pfeifer GP, Steigerwald SD, Mueller PR, Wold B, Riggs AD: Genomic sequencing and methylation analysis by ligation mediated PCR. Science 1989;246:810-813 https://doi.org/10.1126/science.2814502
  20. Singer-Sam J, LeBon JM, Tanguay RL, Riggs AD: A quantitative HpaII-PCR assay to measure methylation of DNA from a small number of cells. Nucl Acids Res 1990;18:687
  21. Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch W, Ahrendt S, Eby Y, Sewell D, Nawroz H, Bartek J, Sidransky D: High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell arcinoma. Cancer Res 1996;56:3630-3633
  22. Peinado MA, Malkhosyan S, Velazquez A, Perucho M: Isolation and characterization of allelic losses and gains in colorectal tumors by arbitrarily primed polymerase chain reaction. Proc Natl Acad Sci U S A 1992;89:10065-10069
  23. Liang G, Salem CE, Yu MC, Nguyen HD, Gonzales FA, Nguyen TT, Nichols PW, Jones PA: DNA methylation differences associated with tumor tissues identified by genome scanning analysis. Genomics 1998;53:260-268 https://doi.org/10.1006/geno.1998.5502
  24. Liang G, Robertson KD, Talmadge C, Sumegi J, Jones PA: The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells. Cancer Res 2000;60:4907-4912
  25. Sambrook J, Fritsch EF, Maniatis T: Molecular cloning : A laboratory manual, Cold spring harbor Lab. NY, 2nd, 1998
  26. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 1996;93:9821-9826
  27. Xiong Z, Laird PW: COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 1997;25:2532-2534 https://doi.org/10.1093/nar/25.12.2532
  28. Kim HS, Chung WB, Hong SH, Kim JA, Na SY, Jang HJ, Sohn YK, Kim JW: Inactivation of p16INK4a in primary tumors and cell lines of head and neck squamous cell carcinoma. Mol Cells 2000;10:557-565 https://doi.org/10.1007/s10059-000-0557-8
  29. Nakayama S, Sasaki A, Mese H, Alcalde RE, Tsuji T, Matsumura T: The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas. Int J Cancer 2001;93:667-673 https://doi.org/10.1002/ijc.1386
  30. Patel K. Follistatin: Int J Biochem Cell Biol 1998;30:1087-1093 https://doi.org/10.1016/S1357-2725(98)00064-8
  31. Young JP, Biden KG, Simms LA, Huggard P, Karamatic R, Eyre HJ, Sutherland GR, Herath N, Barker MA, Anderson GJ, Fitzpatrick D, Ramm GA, Jass JR, Leggett BA: HPP1: a transmembrane protein commonly methylated in colorectal polyps and cancers. Proc Natl Acad Sci USA 2001;98:265-270
  32. Uchida T, Wada K, Akamatsu T, Yonezawa M, Noguchi H, Mizoguchi A: A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB4 in MKN28 gastric cancer cells. Biochem Biophys Res Commun 1999;266:593-602 https://doi.org/10.1006/bbrc.1999.1873