Retinoic Acid reduces migration of human breast cancer cells: Role of Retinoic Acid Receptor Beta.

FLAMINI MARINA INÉS ; GAUNA GISEL VALERIA; SOTTILE MAYRA LIS; NADIN SILVINA BEATRIZ; SANCHEZ ANGEL MATIAS; VARGAS-ROIG LAURA MARÍA

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (PRINT)

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014

1582-1838

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 β (RARβ) 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 RARβ protein participates in the metastatic process. Methodology: T47D and MCF7 breast cancer cells lines were used to perform MTT assay, immunobloting, migration assays, RNA interference and immunofluorescence. Results: Administration of retinoic acid (RA) in breast cancer cells induced RARβ gene expression that was greatest after 72 hours with a concentration 1uM. High concentrations of RA increased the expression of RARβ causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration related proteins (moesin, c-Src and FAK). The treatment with RARα and RARγ agonists did not affect the cell migration. On the contrary, the addition of the selective retinoid RARβ-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition. When RARβ gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c-Src and FAK expressions. Conclusion: RARβ is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration.