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

FLAMINI MARINA INES; GAUNA GISEL; VARGAS ROIG LAURA MARIA

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Breast cancer is the most common malignancy in women producing 98% of deaths when distant metastases occur. Retinoic acid receptor ß (RARß) expression is loss in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis. Our hypothesis is that RARß protein is involved in metastasis process. Objectives: 1)To verify in MCF7 cells (RARß gene methylated and silenced) if the re-expression of the gene, after treatment with retinoic acid (RA), inhibits cell migration. 2) To determine in T47D cells (RARß expressed) if the silencing of this gene increases cell migration. 3) To identify the possible molecular mechanisms by which RA/RARß exerts its effect. Methods: MTT and migration assays, WB, RNA interference and immunofluorescence. Results: Administration of RA in MCF7 cells induces RARß gene expression that is greatest after 72 hours with 1uM concentration. We note that the higher concentration of RAand higher expression of RARß yields a 60% inhibition of cell migration (p <0.01) and significantly decreases the expression of proteins that stimulate the migration (c-Src, moesin and HSP27). When RARß gene silencing is performed, the RA fails to inhibit migration significantly. Conclusion: RARß is necessary to inhibit breast cancer cells migration induced by RA modulating the expression of proteins involved in cell migration/invasion.