RT Journal Article
SR Electronic
T1 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
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 249
OP 257
VO 32
IS 1
A1 NAIR LOPES
A1 JOANA CARVALHO
A1 CECÍLIA DURÃES
A1 BÁRBARA SOUSA
A1 MADALENA GOMES
A1 JOSÉ LUIS COSTA
A1 CARLA OLIVEIRA
A1 JOANA PAREDES
A1 FERNANDO SCHMITT
YR 2012
UL http://ar.iiarjournals.org/content/32/1/249.abstract
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.