Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
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PROMOTER METHYLATION OF THE CDH-13 GENE IN THE ORAL SQUAMOUS CELL CARCINOMA

구강 편평상피암종에서 CDH-13 유전자의 promoter methylation에 대한 연구

  • Lee, Moon-Joo (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University) ;
  • Han, Se-Jin (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University) ;
  • Kim, Kyung-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University)
  • 이문주 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 한세진 (단국대학교 치과대학 구강악안면외과학교실) ;
  • 김경욱 (단국대학교 치과대학 구강악안면외과학교실)
  • Published : 2008.10.31
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Abstract

CDH-13(T-cadherin), which is one of a kind among the 20 cadherins, can be found mainly in wall of aorta, neuron, spleen, blood vessel etc. It is also called H-cadherin. This structural difference can explain that CDH-13 is thought to play a key role in maintaining mutual relation between extra and intra-cellular environment rather than in cell adhesion. The main function of CDH-13 is to participate in blood vessel function. Additionally, it is known to regulate cell growth and cell contact inhibition. When cells are proliferating, cell surface perceives other cells so that substance such as CDH-13 can inhibit their growth or proliferation resulting in homeostasis without endless proliferation or invasion of connective tissue boundaries. However, tumor cell itself appears to be different from normal cells' growth, invasion or transmission. Therefore, it can be diagnosed that these characteristics are closely related to expression of CDH-13 in tumor cells. This study is to investigate expression of CDH-13 in SCC and its correlation with promoter methylation. 20 of tissue species for the study are excised and gathered from 20 patients who are diagnosed as SCC in department of OMS, dental hospital, dankook university. To find development of CDH-13 in each tissue samples, immunohistochemical staining, RT-PCR gene analysis and methylation specific PCR are processed. The results are as follows. 1.Immunohistochemical staining: In normal oral squamous epithelial tissue, strong expression of CDH-13 was found in cell plasma membrane of basal cell layer. On the other hand, in case of low-differentiated oral SCC, development of CDH-13 was hardly seen. 2.The development of CDH-13 gene: In 9 of samples, expression of CDH-13 gene could be seen and 2 of them showed low expression compared to the others. And rest of the 11 samples showed no expression of CDH-13 gene. 3.Methylation of CDH-13 gene: Among 9 samples which expressed CDH-13 gene, 7 of them showed unmethylation. In addition, among 11 samples without CDH-13 gene expression, 10 showed methylation. According to the results stated above, promoter methylation were found in 13 samples(65%) among 20 of oral SCC samples. In low-differentiated SCC, suppression of gene expression could be seen accompanying promoter methylation. These phenomenon of gene expression was proved by immunohistochemical investigation. Finally, for development of oral SCC, conclusions can be made that suppression of CDH-13 played a main role and suppression of gene expression was originated from promoter methylation. Considering this, it is expected that suppression of CDH-13 from promoter methylation to be utilized as a good diagnostic marker of oral SCC.

Keywords

References

  1. Cooper,Hausman : The Cell ; A molecular approach. Sinaur Associates Inc. 2007;4
  2. Takeichi M. : Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251:1451-55 https://doi.org/10.1126/science.2006419
  3. 표성운,김영실,박지영,김창현,이 원,박민규 : 구강 편평세포 암에서 E-cadherin 유전자의 과메틸화 J. Kor. Oral Maxillofac. Surg. 2008; 34:135-140
  4. Behrens J. : The role of cell adhesion molecules in cancer invasion and metastasis. Breast Cancer Res Treat 1994;24:175-84
  5. Ziober BL,Silverman SS,Kramer RH : Adhesive mechanisms regulating invasion and metastasis in oral cancer,Crit. Rev. Oral Biol. Med 2001;12:499-510 https://doi.org/10.1177/10454411010120060401
  6. Oka H,Shiozaki H,Kobayashi K : Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 1993;53:1696-1701
  7. Umbas R,Isaacs WB,Bringuier PP : Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer, Cancer Res 1994;54:3929-33
  8. Umbas R,Schalken JA,Aalders TW : Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer,Cancer Res 1992;52:5104-9
  9. Jiao W,Miyazaki K,Kitajima Y : Inverse correlation between Ecadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo,Br. J. Cancer 2002;86:98-101 https://doi.org/10.1038/sj.bjc.6600017
  10. Graff JR,Greenberg VE,Herman JG : Distinct patterns of E-cadherin CpG island methylation in papillary,follicular,Hurthle's cell,and poorly differentiated human thyroid carcinoma,Cancer Res 1998;58:2063-6
  11. Schipper JH,Frixen UH,Behrens J : E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res 1991;51:6328-37
  12. Rodrigo JP,Dominguez F,Alvarez C : Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features. Eur. J. Cancer 2002;38:1059-64 https://doi.org/10.1016/S0959-8049(01)00399-9
  13. Tkachuk VA,Bochkov VN,Philippova MP : Identification of an atypical lipoprotein-binding protein from human aortic smooth muscle as T-cadherin. FEBS Lett. 1998;421:208-12 https://doi.org/10.1016/S0014-5793(97)01562-7
  14. Philippova MP,Bochkov VN,Stambolsky DV : T-cadherin and signal- transducing molecules co-localize in caveolin-rich membrane domains of vascular smooth muscle cells. FEBS Lett 1998;429:207-10 https://doi.org/10.1016/S0014-5793(98)00598-5
  15. Zhou S,Liang SB,Miyachi Y : Expression of T-cadherin in basal keratinocytes of skin. J Invest Dermatol 2002;118:1080-4 https://doi.org/10.1046/j.1523-1747.2002.01795.x
  16. Ranscht B and Zimmermann D : T-cadherin,a novel cadherin adhesion molecule in the nervous system,lacks the conserved cytoplasmic region. Neuron 1991;7:391-402 https://doi.org/10.1016/0896-6273(91)90291-7
  17. Takeuchi T,Misaki A,Liang SB : Expression T-cadherin in human brain and its characteristics as a negative growth rgulator of EGF in neuroblastoma cells. J Neurochem 2000;74:1489-97 https://doi.org/10.1046/j.1471-4159.2000.0741489.x
  18. Takeuchi T and Ohtsuki Y : Recent progress in T-cadherin (CDH13, H-cadherin) research. Histol Histopathol 2001;16:1287-93
  19. Lee SW : H-cadherin,a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat Med 1996;2:776-82 https://doi.org/10.1038/nm0796-776
  20. Lee SW,Reimer CL,Campbell DB : H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo. Carcinogenesis 1998;19:1157-9 https://doi.org/10.1093/carcin/19.6.1157
  21. Sato M,Mori Y,Sakurada A,Fujimura S : The Hcadherin(CDH13)gene is inactivated in human lung cancer. Hum Genet 1998;103:96-101 https://doi.org/10.1007/s004390050790
  22. Toyooka KO,Toyooka S,Virmani AK : Loss of expression andaberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Res 2001;61:4556-60
  23. Zhong Y,Delgado Y,Gomez J : Loss of H-cadherin protein expression in human non-small cell lung cancer is associated with tumorigenicity. Clin Cancer Res 2001;7:1683-7
  24. Hatta K,Okada TS,Yakeichi M : A monoclonal antibody disrupting calcium-dependent cell-cell adhesion of brain tissues: possible role of its target antigen in animal pattern formation. Proc Natl Acad Sci USA 1985;82:2789-93
  25. Boller K,Vestweber D,Kemler R : Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol 1985;100:327-32 https://doi.org/10.1083/jcb.100.1.327
  26. Ozawa M and Kemler R : Molecular organization of the uvomorulincatenin complex. J Cell Biol 1992;116:989-96 https://doi.org/10.1083/jcb.116.4.989
  27. Rubinfeld B,Souza B,Alvert I : Association of the APC gene product with beta-catenin. Science 1993;262:1731-4 https://doi.org/10.1126/science.8259518
  28. Breen E,Steele G,Mercurio AM : Role of E-cadherin/$\alpha $-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells. Ann Surg Oncol 1995;2:378-85 https://doi.org/10.1007/BF02306369
  29. Caca K,Kolligs FT,Ji X : $\beta$-catenin and ${\gamma}$-catenin mutations,but not E-cadherin inactivation,underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Cell Growth Differ 1999;10:369-376
  30. Mareel M,Boterberg T,Noe V : E-cadherin/catenin/cytoskeleton complex : a regulator of cancer invasion. J Cell Physiol 1997;173:271-4 https://doi.org/10.1002/(SICI)1097-4652(199711)173:2<271::AID-JCP34>3.0.CO;2-G
  31. Takayama T,Shiozaki H,Shibamoto S : $\beta$-Catenin expression in human cancers. Am J Pathol 1996;148:39-46
  32. Shimoyama Y,Nagafuchi A,Fujita S : Cadherin dysfunction in a human cancer cell line:possible involvement of loss of $\alpha$-catenin expression in reduced cell-cell adhesiveness. Cancer Res 1992;52:5770-4
  33. Oyama T,Kanai Y,Ochiai A : A truncated $\beta$-Catenin disrupts the interaction between E-caherin and $\alpha$-catenin: A cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res 1994;54:6282-7
  34. Jawhari A,Jordan S,Poole S : Abnormal immunoreactivity of the Ecadherin- catenin complex in gastric carcinoma: relationship with patient survival. Gastroenterology 1997;112:46-54 https://doi.org/10.1016/S0016-5085(97)70218-X
  35. Chang HW,Chow V,Lam KY : Loss of Ecadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance,Cancer 2002;94;386-92 https://doi.org/10.1002/cncr.10211
  36. Melki JR,Vincent PC,Brown RD : Hypermethylation of E-cadherin in leukemia,Blood 2000;95:3208-13
  37. Nakayama S,Sasaki A,Mese H : The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas,Int. J. Cancer 2001;93:667-73 https://doi.org/10.1002/ijc.1386
  38. Saito Y,Takazawa H,Uzawa K : Reduced expression of E-cadherin in oral squamous cell carcinoma: relationship with DNA methylation of 50 CpG island,Int. J. Oncol 1998;12;293-8
  39. Ivanov D,Philippova M,Antropova J : Expression of cell adhesion molecule T-cadherin in the human vasculature. Histochem. Cell Biol 2001;115:231-42
  40. Resink TJ,Kuzmenko YS,Kern F : LDL binds to surface-expressed human T-cadherin in transfected HEK293 cells and influences homophilic adhesive interactions. FEBS Lett 2000;463:29-34 https://doi.org/10.1016/S0014-5793(99)01594-X
  41. Takeuchi T,Liang SB,Ohtsuki Y : Downregulation of expression of a novel cadherin molecule,T-cadherin,in basal cell carcinoma of the skin. Mol. Carcinog 2003;35:173-9 https://doi.org/10.1002/mc.10088
  42. Toyooka S,Toyooka KO,Harada K : "Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas.". Cancer Res 2002;62:3382-6
  43. Esteller M,Corn PG,Baylin SB,Herman JG : A gene hypermethylation profile of human cancer,Cancer Res 2001;61;3225-9
  44. Tamotsu T,Sheng-Ben,Hiroshi S : Loss of T-cadherin (CDH13,Hcadherin) expression in cutaneous squamous cell carcinoma. Laboratory Investigation 2002;82:1023-9 https://doi.org/10.1097/01.LAB.0000025391.35798.F1
  45. Maruyama R,Toyooka KO,Harada K : "Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features.". Cancer Res 2001;61:8659-63
  46. Kim JS ,Han J,Shim YM : Aberrant Methylation of H-Cadherin (CDH13) Promoter Is Associated with Tumor Progression in Primary Nonsmall Cell Lung Carcinoma. CANCER 2005;104;1825-32 https://doi.org/10.1002/cncr.21409