1Alpha,25-dihydroxyvitamin D3 induces de novo E-cadherin expression in triple-negative breast cancer cells by CDH1-promoter demethylation.
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) (1α,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 1α,25(OH)(2)D(3) effects as a differentiating agent in triple-negative breast cancer cells were assessed.


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)(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.


CONCLUSIONS
Metaplastic carcinomas may respond to 1α,25(OH)(2)D(3), since they express VDR and 1α,25(OH)(2)D(3) induces de novo E-cadherin expression in breast cancer cells by promoter demethylation.
IPATIMUP, Institute of Molecular Pathology and Immunology of University of Porto, Porto, Portugal.
Nair
N
Lopes
Joana
J
Carvalho
Cecília
C
Durães
Bárbara
B
Sousa
Madalena
M
Gomes
José Luis
JL
Costa
Carla
C
Oliveira
Joana
J
Paredes
Fernando
F
Schmitt
D015703:Antigens, CD; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D015703:Antigens, CD; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014807:Vitamin D; C513384:CDH1 protein, human; C118756:dihydroxy-vitamin D3; C508053:ERBB2 protein, human