Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines.
Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines.
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发表时间：
1999-05
期刊：
影响因子：
11.2
通讯作者：
X. C. Xu;Xiao-Mao Liu;Eiichi Tahara;Scott M. Lippman;R. Lotan
中科院分区：
文献类型：
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作者：
X. C. Xu;Xiao-Mao Liu;Eiichi Tahara;Scott M. Lippman;R. Lotan
类维生素A具有化学治疗和化学预防活性，可能是由于它们调节细胞生长、分化和凋亡的能力。这些作用被认为是由核视黄酸（RA）受体（RAR）和类维生素A X受体介导的，每种受体都包括三种亚型（α、β和γ），它们作为转录因子发挥作用。为了确定RARs是否在介导RA对人食管癌（HEC）细胞的作用中发挥作用，我们分析了RA对以下方面的影响：（a）7个HEC细胞系的生长、分化和凋亡;（B）受体表达;（c）RA对受体的调节;以及（d）20个外科HEC标本中受体的表达。RA抑制了7个细胞系中的5个的生长，并且还抑制了所有细胞系中鳞状分化标志物细胞角蛋白1和转氨酶I的组成性表达。RA对上述5种细胞株的生长抑制作用是通过诱导细胞凋亡实现的。所有7个细胞系表达RAR-α和RAR-γ，4个细胞系显示RA的一些变化，但与凋亡无关。与此相反，RAR-β在7个细胞系中的5个中表达，并且在这5个细胞系中被RA上调，这与凋亡相关。两个不表达RAR-β的细胞系显示没有生长抑制或凋亡，也没有RAR-β诱导。有趣的是，只有这两种细胞系能够在软琼脂中形成集落。RAR-α、RAR-β和RAR-γ mRNA在所有20个相邻正常食管组织中表达。RAR-α和RAR-γ的表达在HEC标本中保持阳性，但RAR-β的表达仅在20例HEC标本中的6例中检测到。这些数据表明，RAR-β的表达与HEC细胞对RA的反应有关，RAR-β表达的缺失可能与HEC的发育有关。
Retinoids exhibit chemotherapeutic and chemopreventive activities, possibly due to their ability to modulate cell growth, differentiation, and apoptosis. These effects are thought to be mediated by nuclear retinoic acid (RA) receptors (RARs) and retinoid X receptors, each of which includes three subtypes (alpha, beta, and gamma) that act as transcription factors. To determine whether RARs play a role in mediating the effects of RA on human esophageal cancer (HEC) cells, we analyzed the effects of RA on: (a) the growth, differentiation, and apoptosis in seven HEC cell lines; (b) receptor expression; (c) receptor modulation by RA; and (d) expression of receptors in 20 surgical HEC specimens. RA inhibited the growth of five of seven cell lines and also the constitutive expression of the squamous differentiation markers cytokeratin 1 and transglutaminase I in all cell lines. The growth inhibition by RA was due to the induction of apoptosis in the five cell lines. All seven cell lines expressed RAR-alpha and RAR-gamma, and four cell lines showed some changes by RA, but not associated with apoptosis. In contrast, RAR-beta was expressed in five of seven cell lines and up-regulated by RA in these five cell lines, which were associated with apoptosis. Two cell lines that failed to express RAR-beta showed no growth inhibition or apoptosis and no RAR-beta inducibility. Interestingly, only these two cell lines were able to form colonies in soft agar. RAR-alpha, RAR-beta, and RAR-gamma mRNAs were expressed in all 20 adjacent normal esophageal tissues. The expression of RAR-alpha and RAR-gamma remains positive in HEC specimens, but RAR-beta expression was detected in only 6 of 20 HEC specimens. These data suggest that the expression of RAR-beta is associated with response of HEC cells to RA and that the loss of RAR-beta expression may be associated with HEC development.