PT - JOURNAL ARTICLE AU - NAIR LOPES AU - JOANA CARVALHO AU - CECÍLIA DURÃES AU - BÁRBARA SOUSA AU - MADALENA GOMES AU - JOSÉ LUIS COSTA AU - CARLA OLIVEIRA AU - JOANA PAREDES AU - FERNANDO SCHMITT TI - 1Alpha,25-dihydroxyvitamin D<sub>3</sub> Induces <em>de novo</em> E-cadherin Expression in Triple-negative Breast Cancer Cells by <em>CDH1</em>-promoter Demethylation DP - 2012 Jan 01 TA - Anticancer Research PG - 249--257 VI - 32 IP - 1 4099 - http://ar.iiarjournals.org/content/32/1/249.short 4100 - http://ar.iiarjournals.org/content/32/1/249.full SO - Anticancer Res2012 Jan 01; 32 AB - Background: The triple-negative subgroup of breast cancer includes a cluster of tumors exhibiting low E-cadherin expression (metaplastic carcinomas). In several cancer models, 1alpha,25-dihydroxyvitamin D3 (1α,25(OH)2D3) induces differentiation by increasing E-cadherin expression. The Vitamin D receptor (VDR) was evaluated as a possible therapeutic target for metaplastic carcinomas and 1α,25(OH)2D3 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, 1α,25(OH)2D3 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 1α,25(OH)2D3, since they express VDR and 1α,25(OH)2D3 induces de novo E-cadherin expression in breast cancer cells by promoter demethylation.