Monzon R I, Fillmore C, Hudson L G
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, Illinois 60611, USA.
Mol Pharmacol. 1997 Mar;51(3):377-82.
Nuclear receptors for retinoic acid are important modulators of epidermal cell proliferation and terminal differentiation. Aberrant expression of retinoic acid receptors (RARs) and retinoid X receptors in the epidermis has been associated with altered differentiation capacity and tumor progression. In this study, we describe a human squamous cell carcinoma line, SCC 12F, which displays reduced RARgamma expression and diminished responsiveness to retinoic acid. When compared with normal keratinocytes or other squamous cell carcinoma lines that display normal levels of RARgamma, several measures of cellular response to retinoic acid are altered in SCC 12F cells, including inhibition of cornified envelope formation, reduction of involucrin mRNA expression, and transcriptional regulation of the involucrin gene. Normal patterns of ligand-dependent transcriptional response were restored upon co-transfection of an expression vector containing either RARalpha or RARgamma. Our findings demonstrate that reduced expression of RAR may have direct functional consequences with regard to keratinocyte differentiation and that the defect may be alleviated by reintroduction of functional receptor.
维甲酸核受体是表皮细胞增殖和终末分化的重要调节因子。表皮中维甲酸受体（RARs）和类视黄醇X受体的异常表达与分化能力改变和肿瘤进展有关。在本研究中，我们描述了一种人鳞状细胞癌系SCC 12F，其RARγ表达降低且对维甲酸的反应性减弱。与显示正常水平RARγ的正常角质形成细胞或其他鳞状细胞癌系相比，SCC 12F细胞中几种对维甲酸的细胞反应指标发生了改变，包括抑制角质包膜形成、降低内披蛋白mRNA表达以及内披蛋白基因的转录调控。当共转染含有RARα或RARγ的表达载体时，配体依赖性转录反应的正常模式得以恢复。我们的研究结果表明，RAR表达降低可能对角质形成细胞分化有直接的功能影响，并且通过重新引入功能性受体可以缓解该缺陷。
