Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta.
Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta.
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DOI：
10.1111/jcmm.12256
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发表时间：
2014-06
影响因子：
5.3
通讯作者：
Vargas-Roig LM
中科院分区：
文献类型：
--
作者：
Flamini MI;Gauna GV;Sottile ML;Nadin BS;Sanchez AM;Vargas-Roig LM
乳腺癌是女性最常见的恶性肿瘤，98%的病例死于远处转移。维甲酸受体β(RARβ)在50%的浸润性乳腺癌组织中不表达，与淋巴结转移有关。我们的假设是RARβ蛋白参与了肿瘤的转移过程。用T47D和MCF7乳腺癌细胞株进行存活率测定、免疫印迹试验、迁移试验、RNA干扰和免疫荧光试验。维甲酸(RA)诱导乳腺癌细胞RARβ基因表达，浓度为1：1的μM作用72小时后表达最强。高浓度RA使RARβ表达增加，细胞迁移抑制60%，并显著降低迁移相关蛋白[moesin，c-src和粘着斑激酶]的表达。RARα和RARγ激动剂处理不影响细胞迁移。相反，添加选择性的维甲酸受体β激动剂(BMS453BMS453)显著减少细胞迁移，与RA抑制相当。当RA受体β基因沉默时，RA不能显著抑制迁移，导致不能有效地减少Moesin、c-Src和FAK的表达。RARβ是抑制维甲酸诱导的乳腺癌细胞迁移所必需的，它调控细胞迁移相关蛋白的表达。
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.