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类视黄醇X受体在JEG-3绒毛膜癌细胞中高表达:参与类视黄醇对细胞功能的调节

High retinoid X receptor expression in JEG-3 choriocarcinoma cells: involvement in cell function modulation by retinoids.

作者信息

Guibourdenche J, Roulier S, Rochette-Egly C, Evain-Brion D

机构信息

Unité INSERM 427, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes, France.

出版信息

J Cell Physiol. 1998 Sep;176(3):595-601. doi: 10.1002/(SICI)1097-4652(199809)176:3<595::AID-JCP16>3.0.CO;2-Z.

DOI:10.1002/(SICI)1097-4652(199809)176:3<595::AID-JCP16>3.0.CO;2-Z
PMID:9699512
Abstract

Retinoic acid (RA) is an important mediator of cell differentiation. It stimulates hCG secretion by JEG-3 choriocarcinoma cells in vitro after a time lag. The first aim of this study was to characterize which types of retinoid receptors (RARs and RXRs) are present in JEG-3 cells. Using Western blot analysis and immunocytochemistry with specific antibodies as well as Northern blot analysis, we found that JEG-3 cells expressed RAR alpha and RXR alpha, the latter being the predominant receptor. We then analyzed the action on cell proliferation and hCG secretion of the physiological retinoids all-trans RA (RA) and 9 cis RA as well as synthetic retinoids with specific affinity for RAR alpha and RXR alpha. All these retinoids were potent inhibitors of cell growth, maximal inhibition (72 +/- 2%) being observed after 4 days of treatment with Ro 25, a RXR alpha specific ligand. Within 24 h, 9 cis RA and Ro 25 stimulated hCG secretion, and maximal stimulation (1,472 +/- 10%) occurred at 48 h with the RXR alpha-specific ligand. The RAR alpha-specific ligand also stimulated hCG secretion but to a lower extend and after a delay of 48 h. These results suggest a predominant role of RXR alpha in mediating the biological effects of retinoids on JEG-3 cells and the possible induction by RA itself of the metabolic pathway leading to 9 cis RA.

摘要

视黄酸(RA)是细胞分化的重要介质。体外培养时,它经过一段时间的延迟后刺激JEG - 3绒毛膜癌细胞分泌人绒毛膜促性腺激素(hCG)。本研究的首要目的是确定JEG - 3细胞中存在哪些类型的类视黄醇受体(RARs和RXRs)。通过蛋白质免疫印迹分析、使用特异性抗体的免疫细胞化学以及Northern印迹分析,我们发现JEG - 3细胞表达RARα和RXRα,后者是主要的受体。然后,我们分析了生理性类视黄醇全反式视黄酸(RA)和9顺式视黄酸以及对RARα和RXRα具有特异性亲和力的合成类视黄醇对细胞增殖和hCG分泌的作用。所有这些类视黄醇都是细胞生长的有效抑制剂,在用RXRα特异性配体Ro 25处理4天后观察到最大抑制(72±2%)。在24小时内,9顺式视黄酸和Ro 25刺激hCG分泌,使用RXRα特异性配体时,在48小时出现最大刺激(1472±10%)。RARα特异性配体也刺激hCG分泌,但程度较低且延迟48小时。这些结果表明RXRα在介导类视黄醇对JEG - 3细胞的生物学效应中起主要作用,并且RA本身可能诱导导致9顺式视黄酸的代谢途径。

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