Introduction: Disease recurrence is an important obstacle in estrogen receptor positive (ER) tamoxifen treated breast carcinoma patients. Tamoxifen resistance-related molecular mechanisms are not fully understood. Alteration in DNA methylation which contributes to transcriptional regulation of cancer-related genes plays a crucial role in tamoxifen response. In the present study, the contribution of promoter methylation and mRNA expression of and in the development of breast carcinoma and tamoxifen refractory was assessed.
Methods: Methylation specific-high resolution melting (MS-HRM) analysis and Real-time quantitative PCR (RT-qPCR) experiment were performed to analyze the promoter methylation and mRNA expression levels of and genes in 102 breast tumors and adjacent normal breast specimens.
Results: We indicated that PAX2 expression is decreased in breast tissues due to hypermethylation in its promoter region. Compared to the adjacent normal tissues, the tumors exhibited significantly lower relative mRNA levels of and increased expression of . Aberrant promoter methylation of and overexpression of was observed in tamoxifen resistance patients compared to the sensitive ones. Cox regression analysis exhibited that the increased promoter methylation status of and overexpression of remained as unfavorable identifiers which influence patients' survival independently.
Conclusions: Our results revealed that the aberration in promoter methylation and overexpression are associated with the tamoxifen response in breast carcinoma patients. Further research is needed to demonstrate the potential of using and expression and their methylation-mediated regulation as predictive or prognostic biomarkers or as a new target therapy for better disease management.
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