RESUMEN
Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
Asunto(s)
Femenino , Humanos , Anoicis , Neoplasias de la Mama , Genética , Metabolismo , Patología , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Factor de Crecimiento del Tejido Conjuntivo , Metabolismo , Metilación de ADN , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , MicroARNs , Genética , Metabolismo , Metástasis de la Neoplasia , Proteínas de Unión al GTP rho , Metabolismo , Quinasas Asociadas a rho , MetabolismoRESUMEN
AIM: This study is designed to demonstrate the drug resistance breast cancer cell line MCF-7/ADM has a higher proportion of cancer stem cells than its original parent cell line MCF-7 in vitro.METHODS: Firstly,the drug resistance of MCF-7/ADM was estimated by MTT method,and then higher proportion of cancer stem cells in MCF-7/ADM than that in MCF-7 was demonstrated by three aspects: side population analysis,sphere culture and cell surface markers of breast cancer stem cells.RESULTS: The drug resistance index of MCF-7/ADM compared to MCF-7 was 37.1.The proportion of side population in MCF-7/ADM and MCF-7 was 9.60%?0.66% versus 0.39%?0.11%;The proportion of sphere-initiating cells in MCF-7/ADM and MCF-7 was 10.27%?0.64% versus 1.03%?0.15%,and the proportion of CD+44CD-24 cells in these two cell lines was 64.87%?3.87% versus 3.70%?0.53%,all are statistically significant.CONCLUSION: ADM resistance breast cancer cell line MCF-7/ADM has a higher proportion of cancer stem cells than that in its original cell line MCF-7.