1Alpha,25-dihydroxyvitamin D3 induces de novo E-cadherin expression in triple-negative breast cancer cells by CDH1-promoter demethylation.

摘要

BACKGROUND: The triple-negative subgroup of breast cancer includes a cluster of tumors exhibiting low E-cadherin expression (metaplastic carcinomas). In several cancer models, 1 alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) induces differentiation by increasing E-cadherin expression. The Vitamin D receptor (VDR) was evaluated as a possible therapeutic target for metaplastic carcinomas and 1alpha,25(OH)(2)D(3) effects as a differentiating agent in triple-negative breast cancer cells were assessed. MATERIALS AND METHODS: Metaplastic carcinomas were assessed for VDR expression by immunohistochemistry; differences in E-cadherin expression in triple-negative breast cancer cells were evaluated by real-time PCR, western blotting and Cadherin 1 (CDH1) methylation status. RESULTS: Most of the metaplastic carcinomas were positive for VDR expression. Furthermore, 1alpha,25(OH)(2)D(3) promoted differentiation of MDA-MB-231 cells by inducing de novo E-cadherin expression, an effect that was time- and dose-dependent. Also, E-cadherin expression was due to promoter demethylation. CONCLUSION: Metaplastic carcinomas may respond to 1alpha,25(OH)(2)D(3), since they express VDR and 1alpha,25(OH)(2)D(3) induces de novo E-cadherin expression in breast cancer cells by promoter demethylation.