Downregulation of E-cadherin expression in breast cancer by promoter hypermethylation and its relation with progression and prognosis of tumor


Shargh S. A., Sakizli M., Khalaj V., Movafagh A., Yazdi H., Hagigatjou E., ...More

MEDICAL ONCOLOGY, vol.31, no.11, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 11
  • Publication Date: 2014
  • Doi Number: 10.1007/s12032-014-0250-y
  • Journal Name: MEDICAL ONCOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: Breast cancer, Methylation, E-cadherin, Progression, Prognosis, THERAPEUTIC TARGET, PROTEIN EXPRESSION, GENE, METHYLATION, REGION, MECHANISMS, CARCINOMA
  • Dokuz Eylül University Affiliated: Yes

Abstract

Breast cancer is the most common cancer in women around the world, and novel prognosis strategies is needed to control more accurate and effective of this malignant disease. Among the latest prognostic markers is E-cadherin, which mediates cell-cell adhesion by associating with catenins. Loss of E-cadherin gene (CDH1) function by genetic or epigenetic alteration leads to tumorigenesis. The aim of our study was to investigate E-cadherin gene promoter methylation in breast cancer, and its correlation with E-cadherin protein expression. Fifty primary breast cancers tissue with ductal type and 50 normal breast sample from the same patients that was located adjacent to tumor region as controls were provided by Imam Reza-based referral and teaching hospital affiliated to Tabriz University of Medical Sciences, Tabriz, Iran. CDH1 promoter region CpG sites methylation and E-cadherin protein expression were determined by bisulfitespecific polymerase chain reaction and Western blot analysis, and the resulting products were sequenced on an ABI automated sequencer for firm conclusion. CDH1 hypermethylation in breast tumor specimen (ductal type) was observed in 94 % (47 of 50) comparing with normal samples methylation, and the significant difference was (p = 0.000). Protein expression in tumor samples tends to diminish with the CDH1 promoter region methylation. In the group of 50 ductal carcinomas cases, most of the cases showing CDH1 hypermethylation correlated inversely with the reduced levels of expression of E-cadherin proteins (95 % of full-methylated tumor samples had no protein expression, and 4.5 % of them had weak expression levels). Possible association was observed between CDH1 methylation and its protein expression (p = 0.000). The results of methylation analysis in promoter region in ten CpG sites (863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) suggested that abnormal CDH1 methylation occurs in high frequencies in ductal breast tumors probably sounds the process of carcinogenesis progression.