Expression of nuclear retinoic acid receptors in normal tracheobronchial cells and in lung carcinoma cells.
Expression of nuclear retinoic acid receptors in normal tracheobronchial cells and in lung carcinoma cells.
复制标题
核视黄酸受体在正常气管支气管细胞和肺癌细胞中的表达。
DOI：
10.1016/0014-4827(91)90512-s
复制
发表时间：
1991
影响因子：
3.7
通讯作者：
A. M. Jetten
中科院分区：
文献类型：
--
作者：
Clara Nervi;T. Vollberg;M. D. George;Arthur Zelent;P. Chambon;A. M. Jetten
维甲酸是气管、支气管壁上皮细胞生长和分化的重要调节因子。为了确定维甲酸类化合物在这些细胞中的作用机制，我们开始检测核维甲酸受体(RARs)在正常人和兔气管支气管上皮细胞(HBE和RBTE)以及几种肺癌细胞系中的表达。在这些细胞中发现了一种特殊的核RAR结合活性，其相对分子质量为50,000。几种维甲酸与这种RAR的结合与它们抑制转谷氨酰胺酶I型活性的能力之间存在相关性。正常HBE和RBTE细胞分别含有2.6kb和3.5kb的RARα转录本和3.1kb的RARγ转录本。在HBE细胞中未检测到RARβ转录本。RAR在鳞状细胞分化过程中的表达无明显变化。100nMretinoic酸处理HBE和RBTE细胞后，RARβ的表达增加，但不改变RARα和RARγ的水平。相反，维甲酸抑制了这些细胞中总蛋白、转谷氨酰胺酶I型和SQ37mRNA的水平。与正常的HBE细胞相比，某些肺癌细胞系的RARβ和RARγ的表达似乎发生了变化。人支气管成纤维细胞表达与人支气管成纤维细胞大小相同的RARα和RARγ转录本。HBF细胞含有2.9kb和3.3kb RARβ基因的低水平表达。用维甲酸处理HBF细胞后，RARβ的表达水平呈时间依赖性增加，最大诱导倍数约为15倍。在这些发现的基础上，我们假设RARs参与抑制气管、支气管上皮细胞的鳞状分化，肺成纤维细胞是维甲酸的靶细胞。
Retinoids are important regulators of the growth and differentiation of tracheobronchial epithelial cells. To determine the mechanism of action of retinoids in these cells, we began to examine the expression of nuclear retinoic acid receptors (RARs) in normal human and rabbit tracheobronchial epithelial (HBE and RbTE, respectively) cells and in several lung carcinoma cell lines. A specific nuclear RAR-binding activity with a molecular weight of 50,000 was identified in these cells. A correlation was found between the binding of several retinoids to this RAR and their ability to inhibit transglutaminase Type I activity. Normal HBE and RbTE cells contained two RARα mRNA transcripts, 2.6 and 3.5 kb in size, and one 3.1 kb RARγ transcript. RARβ transcripts were undetectable in HBE cells. RAR expression was unchanged during squamous differentiation. Treatment of HBE and RbTE cells with 100 nMretinoic acid increased RARβ mRNA expression but did not change the levels of RARα and RARγ. In contrast, retinoic acid suppressed in these cells the level of involucrin, transglutaminase Type I, and SQ37 mRNA. In comparison with normal HBE cells, certain lung carcinoma cell lines appear to have an altered expression of RARβ and RARγ. Human bronchial fibroblasts (HBF) expressed RARα and RARγ transcripts of the same size as HBE cells. HBF cells contain low levels of a 2.9- and 3.3-kb RARβ mRNA. Treatment of HBF cells with retinoic acid increased the level of RARβ mRNA in a time dependent manner; the maximal induction was about 15-fold. On the basis of these findings we hypothesize that RARs are involved in the suppression of squamous differentiation in tracheobronchial epithelial cells and that lung fibroblasts are target cells for retinoids.
影响因子：
2.9
作者：
DUGAICZYK, A;HARON, JA;SCHWARTZ, RJ
通讯作者：
SCHWARTZ, RJ