Biological Function of Retinoic Acid Receptors in Bronchopulmonary System

目的：研究维甲酸受体（retinoic acid receptor， RAR） α和β的表达，以了解维甲酸在支气管肺系统发育和功能中的作用。结果：Northern blot结果显示，RARalpha在成人肺、大鼠和新生儿肺中均有表达。这些数据提示RA和rar α在支气管肺系统发育和功能中的重要作用。另一方面，Northern blot分析显示，在人成年肺、大鼠新生肺和成年肺中均未检测到RARbeta基因的表达。这一数据提示了RARbeta基因的组织特异性表达。rrbeta基因位于3号染色体短臂，利用RNAse保护实验研究了rrbeta基因在人肺癌细胞系中的表达和结构异常。在人肺癌细胞系中未检测到RARbeta基因的表达。这一发现提示RARbeta表达的缺失可能是人类肺癌发生发展过程中一个非常重要的特征。在未来，研究RA和/或RAR是否可能抑制RA和/或RAR细胞的转化，以及RA和/或RAR是否可能逆转癌细胞的转化表型，是重要的显示RA-RAR系统临床应用的可能性。

Purpose: In this study, the expression of retinoic acid receptor(RAR) alpha and beta was examined in order to understand the role of retinoic acid(RA) in the development and function of bronchopulmonary system.Result: RARalpha was shown to be expressed in human adult lung, and rat adult and newborn lung in Northern blot analysis. This data suggested the important role of RA and RARalpha in the development and function of bronchopulmonary system. On the other hand, the expression of RARbeta gene was not detected in human adult lung, and rat newborn and adult lung in Northern blot analysis. This data suggested the tissue-soecific expression of RARbeta gene. Expression and structural abnormality of RARbeta gene was studied in human lung cancer cell lines using RNAse protection assay, since RARbeta gene was known to be located in the short arm of chromosome 3. No expression of RARbeta gene was detected in human lung cancer cell lines. This finding suggested that the loss of the RARbeta expression could be a very important feature in the process of carcinogenesis and progression of human lung cancer.In the future, it is important show the possibility of the clinical application of the RA-RAR system by studying whether it is possible to inhibit the transformation of cells with RA and/or RAR, and whether it is possible to reverse the transformed phenotype of cancer cells with RA and/or RAR.