Relationship between the berrant hypermethylation profile of 14-3-3 sigma and its reduced transcription levels in Chinese women sporadic breast carcinogenesis

摘要

Objective: To study the relationship between 14-3-3 sigma gene promoter hypermethylation and its transcription levels in sporadic breast carcinogenesis. Methods: Hypermethylation of 14-3-3 sigma gene was detected by sensitive MSP assay in carcinous, non-cancerious and normal tissue, and its mRNA was also detected by real-time PCR based on SYBR Green 1. Results: The hypermethylation frequencies of 14-3-3 sigma were 90% in 68 cases of sporadic breast cancer patients. Hypermethylation was presented in portions (2/13,18%) of hyperplastic samples, and no hypermethylation was presented in normal tissue. The hypermethylation 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 hypermethylation of 14-3-3 sigma showed reverse relationship with its mRNA transcription (P < 0.05). Only lymph node metastases was strongly associated with poor outcome (P = 0.02). Whether 14-3-3 sigma promoter methylation or not did not affect the 5-year survival rate of sporadic breast cancer (P > 0.05). Conclusion: Epigenetics alterations of the 14-3-3 sigma can contribute to reducing or losing the expression of 14-3-3 sigma protein, which plays an important role in the development of sporadic breast carcinomas including various types, grades and lymph node metastases.