Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta

Breast cancer is the most common malignancy in women and the appearance of distant metastases produces the death in 98% of cases. The retinoic acid receptor (RAR) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis. Our hypothesis is that RAR protein participates in the metastatic process. T47D and MCF7 breast cancer cell lines were used to perform viability assay, immunobloting, migration assays, RNA interference and immunofluorescence. Administration of retinoic acid (RA) in breast cancer cells induced RAR gene expression that was greatest after 72hrs with a concentration 1M. High concentrations of RA increased the expression of RAR causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration-related proteins [moesin, c-Src and focal adhesion kinase (FAK)]. The treatment with RAR and RAR agonists did not affect the cell migration. On the contrary, the addition of the selective retinoid RAR-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition. When RAR gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c-Src and FAK expressions. RAR is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration.