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Influence of Retinoic Acid on Adhesion Complexes in Human Hepatoma Cells: A Clue to Its Antiproliferative Effects

机译:维甲酸对人肝癌细胞黏附复合物的影响:其抗增殖作用的线索

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Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherin/β-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of β-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.
机译:维甲酸在正常和转化的体外肝细胞中发挥抗增殖和分化作用。为了验证这些作用是否与粘附分子的调节有关,我们使用蛋白质印迹分析和免疫荧光显微镜研究了E-cadherin /β-catenin复合物,粘附连接的主要系统以及occludin / ZO-1视黄酸存在或不存在下培养的HepG2细胞紧密连接中存在的复合物。结果表明,视黄酸处理可通过降低酪氨酸磷酸化水平来增加与E-钙粘蛋白结合的β-连环蛋白的量。通过紧密连接系统获得了相似的结果,其中通过类似的机制降低了酪氨酸上的ZO-1磷酸化水平,增加了occludin / ZO-1复合物的量。免疫荧光图像也证实了这些结果,显示了两种粘附复合物在细胞表面的定位。它们插入质膜可能暗示肝癌细胞中粘附和紧密连接的最佳重组和功能,表明视黄酸除抑制细胞增殖外,还改善细胞与细胞的粘附,维持或诱导更分化的表型的表达。 。

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