Browse > Article
http://dx.doi.org/10.7314/APJCP.2012.13.4.1557

Clinical Outcomes of Downregulation of E-cadherin Gene Expression in Non-small Cell Lung Cancer  

Zheng, Shi-Ying (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University)
Hou, Jing-Yu (The First Affiliated Hospital of Xinxiang Medical University)
Zhao, Jun (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University)
Jiang, Dong (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University)
Ge, Jin-Feng (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University)
Chen, Sheng (Huaian No.1 People's Hospital, Nanjing Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1557-1561 More about this Journal
Abstract
Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods: Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. Conclusion: These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.
Keywords
E-cadherin gene; mRNA expression; paracarcinoma; methylation; non-small cell lung cancer;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Mountain CF (1997). Revisions in the international system for staging lung cancer. Chest, 111, 1710-7.   DOI   ScienceOn
2 Oka H, Shiozaki H, Kobayashi K, et al (1993). Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res, 53, 1696-701.
3 Schipper JH, Frixen UH, Behrens J, et al (1991). E-cadherin expression in squamous cell carcinomas of head and neck: Inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res, 51, 6328-37.
4 Shimoyama Y, Hirohashi S (1991). Cadherin intercellular adhesion molecule in hepatocellular carcinomas: Loss of E-cadherin expression in an undifferentiated carcinoma. Cancer Lett, 57, 131-5.   DOI   ScienceOn
5 Shimoyama Y, Hirohashi S (1991). Expression of E- and P-cadherin in gastric carcinomas. Cancer Res, 51, 2185-92.
6 Shiozaki H, Tahara H, Oka H, et al (1991). Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol, 139, 17-23.
7 Tamura G, Yin J, Wang S, et al (2000). E-cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst, 92, 569-73.   DOI   ScienceOn
8 Tamura G, Yin J, Wang S, et al (2000). E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst (Bethesda), 92, 569-73.
9 Tsao SW, Liu Y, Wang X, et al (2003). The association of E-cadherin expression and the methylation status of the E-cadherin gene in nasopharyngeal carcinoma cells. Eur J Cancer, 39, 524-31.   DOI   ScienceOn
10 Yoshiura K, Kanai Y, Ochiai A, et al (1995). Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA, 9, 7416-9.
11 Zhang HT, Chen XF, Wang MH, et al (2004). Defective expression of transforming growth factor beta receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer. Clin Cancer Res, 10, 2359-67.   DOI
12 Zochbauer-Muller S, Fong KM, Virmani AK, et al (2001). Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 2001 Jan 1;61(1):249-55.
13 Alves CC, Carneiro F, Hoefler H, et al (2009). Role of the epithelialmesenchymal transition regulator Slug in primary human cancers. Front Biosci, 14, 3035-50.
14 Cheng CW, Wu PE, Yu JC, et al (2001). Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 20, 3814-23.   DOI
15 Berx G, Becker KF, Hofler H, et al (1998). Mutations of the human E-cadherin (CDH1) gene. Hum Mutat, 12, 226-37.   DOI   ScienceOn
16 Birchmeier W, Behrens J (1994). Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta, 1198, 11-26.
17 Chen CL, Liu SS, Ip SM, et al (2003). E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours. Eur J Cancer, 39, 517-23.   DOI
18 Corn PG, Heath EI, Heitmiller R, et al (2001). Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res, 7, 2765-9.
19 Esteller M (2002). The coming of age of DNA methylation in medicine in the genomics and postgenomics era. Clin Immunol, 103, 213-6.   DOI
20 Fei QY, Zhang HT, Chen XF, et al (2002). Defected expression of E-cadherin in non-small cell lung cancer. Lung Cancer, 37, 142-52.
21 Gamallo C, Palacios J, Suarez A, et al (1993). Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol, 142, 987-93.
22 Graff JR, Herman JG, Lapidus RG, et al (1995). E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res, 55, 5195-9.
23 Guarino M (2007). Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol, 12, 2153-60.
24 Kanai Y, Ushijima S, Hui AM, et al (1997). The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas. Int J Cancer, 71, 355-9.   DOI   ScienceOn
25 Herman JG, Graff JR, Myohanen S, et al (1996). Methylationspecific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA, 93, 9821-6.   DOI   ScienceOn
26 Hirohashi S (1998). Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol, 153, 333-9.   DOI
27 Hiraguri S, Godfrey T, Nakamura H, et al (1998). Mechanisms of inactivation of E-cadherin in breast cancer cell lines. Cancer Res, 58, 1972-7.
28 Kase S, Sugio K, Yamazaki K, et al (2000). Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res, 6, 4789-96.
29 Leonhardt H, Cardoso MC (2000). DNA methylation, nuclear structure, gene expression and cancer. J Cell Biochem, 35, 78-83.
30 Li LC. Zhao H. Nakajima K, et al (2001). Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer. J Urol, 166, 705-9.   DOI   ScienceOn
31 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T) Method. Methods, 25, 402-8.   DOI   ScienceOn
32 Machado JC, Oliveira C, Carvalho R, et al (2001). E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene, 20, 1525-8.   DOI
33 Margineanu E, Cotrutz CE, Cotrutz C (2008). Correlation between E-cadherin abnormal expressions in different types of cancer and the process of metastasis. Rev Med Chir Soc Med Nat Iasi, 112, 432-6.