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

• Published in: Journal of cellular and molecular medicine 2014-06, Vol.18 (6), p.1113-1123
• Main Authors: Flamini, Marina Inés, Gauna, Gisel Valeria, Sottile, Mayra Lis, Nadin, Beatriz Silvina, Sanchez, Angel Matias, Vargas‐Roig, Laura María
• Format: Article
• Language: English
• Subjects: Acids; Actin Cytoskeleton; Agonists; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Blotting, Western; Breast cancer; breast cancer cells; Breast carcinoma; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Cell adhesion & migration; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Clinical trials; DNA methylation; Epigenetics; FAK; Female; Fluorescent Antibody Technique; Focal adhesion kinase; Focal Adhesion Kinase 1 - metabolism; Gene expression; Gene silencing; Humans; Immunoenzyme Techniques; Immunofluorescence; Inhibition; Invasiveness; Kinases; Lymph nodes; Malignancy; Medical prognosis; Medical research; Metastases; Metastasis; Microfilament Proteins - metabolism; Moesin; Motility; Original; Prevention; Proteins; RARβ; Receptors, Retinoic Acid - antagonists & inhibitors; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Retinoic acid; Retinoids - pharmacology; RNA, Small Interfering - genetics; RNA-mediated interference; Src protein; src-Family Kinases - metabolism; Tretinoin - pharmacology; Tumor cell lines; Tumor Cells, Cultured; Tumors; Viability
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12256

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. 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 RARβ gene expression that was greatest after 72 hrs with a concentration 1 μM. 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 focal adhesion kinase (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. RARβ is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration.