Aberrant methylation profile of 14-3-3 sigma and its reduced transcription/expression levels in Chinese sporadic female breast carcinogenesis

Med Oncol. 2010 Sep;27(3):791-7. doi: 10.1007/s12032-009-9287-8. Epub 2009 Aug 14.

Abstract

To study the relation of 14-3-3 sigma gene promoter hypermethylation and its transcription expression levels in sporadic breast carcinogenesis. Methylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerous, and normal tissue, and its mRNA was also detected by real time PCR based on SYBR Green 1 as well, and protein was detected by west blotting assay. The methylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Methylation was presented in portions (2/13, 18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The methylation change of 14-3-3 sigma gene was markedly related with various types, grades, and lymph node metastases (P < 0.05), and no significant differences in methylation frequencies were seen between premenopause and postmenopause (P > 0.05). The methylation of 14-3-3 sigma shows reverse relation with its mRNA transcription and expression level (P < 0.05). Only was lymph node metastases strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5 years survival rate of sporadic breast cancer patients (P > 0.05). Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing expression of 14-3-3 sigma protein, which play an important role in the development of sporadic breast carcinomas and involved in various types, grades, and lymph node metastases. Otherwise, node metastases of breast carcinogenesis patients are strongly associated with poor outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / biosynthesis
  • 14-3-3 Proteins / genetics*
  • 14-3-3 Proteins / physiology
  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / physiology
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma / chemistry
  • Carcinoma / ethnology
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic / genetics*
  • China / epidemiology
  • CpG Islands / genetics*
  • DNA Methylation*
  • DNA, Neoplasm / analysis*
  • Epithelial Cells / metabolism
  • Exonucleases / biosynthesis
  • Exonucleases / genetics*
  • Exonucleases / physiology
  • Exoribonucleases
  • Female
  • Fibrocystic Breast Disease / genetics
  • Fibrocystic Breast Disease / metabolism
  • Fibrocystic Breast Disease / pathology
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Silencing*
  • Humans
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human