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 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.
Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentina, Mendoza, Argentina.
Marina Ines
MI
Flamini
Gisel Valeria
GV
Gauna
Mayra Lis
ML
Sottile
Beatriz Silvina
BS
Nadin
Angel Matias
AM
Sanchez
Laura Maria
LM
Vargas-Roig
D008841:Actin Cytoskeleton; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000081247:CSK Tyrosine-Protein Kinase; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008840:Microfilament Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082925:retinoic acid receptor beta; C071058:moesin; D014212:Tretinoin; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human; C402892:BMS453
FAK; RARβ; breast cancer cells; cell migration; moesin; retinoic acid