Lee H Y, Chung H Y, Kim K H, Lee J J, Kim K W
Department of Molecular Biology, Pusan National University, Korea.
J Cancer Res Clin Oncol. 1994;120(9):513-8. doi: 10.1007/BF01221027.
The effects of the triterpene acids, ursolic acid and oleanolic acid, on the differentiation of F9 teratocarcinoma stem cells were studied. These agents caused the morphological change of F9 cells into endoderm cells, as did retinoic acid (RA). Moreover, expression of laminin B1, type IV collagen and retinoic acid receptor beta (RAR beta) increased in ursolic- and oleanolic-acid treated F9 cells. Since these agents are structurally similar to the glucocorticoid hormone, we studied the effects of dexamethasone, a synthetic glucocorticoid, on F9 cells. Dexamethasone also induced the morphological change and altered the expression of laminin B1, type IV collagen, and RAR beta in F9 cells. In addition, transcription of glucocorticoid receptor was detected after treatment with these three agents. According to Southwestern blot analysis, a 94-kDa protein, thought to be a glucocorticoid receptor, was detected in F9 cells treated with these agents. In a gel-shift assay, we identified protein factors binding to the glucocorticoid-responsive element (GRE) in the nuclear proteins from F9 cells treated with ursolic or oleanolic acid. The binding activity of the GRE-binding protein disappeared on the addition of unlabeled GRE oligonucleotide. Taken together, these results suggest that UA and OA can induce the differentiation of F9 cells and may regulate the expression of differentiation-specific genes, probably by forming a complex with the glucocorticoid receptor or its analogous nuclear receptor.
研究了三萜酸（熊果酸和齐墩果酸）对F9畸胎瘤干细胞分化的影响。这些试剂导致F9细胞形态转变为内胚层细胞，视黄酸（RA）也有此作用。此外，在经熊果酸和齐墩果酸处理的F9细胞中，层粘连蛋白B1、IV型胶原蛋白和视黄酸受体β（RARβ）的表达增加。由于这些试剂在结构上与糖皮质激素相似，我们研究了合成糖皮质激素地塞米松对F9细胞的影响。地塞米松也诱导了F9细胞的形态变化，并改变了层粘连蛋白B1、IV型胶原蛋白和RARβ的表达。此外，用这三种试剂处理后检测到糖皮质激素受体的转录。根据蛋白质印迹分析，在用这些试剂处理的F9细胞中检测到一种94 kDa的蛋白质，被认为是糖皮质激素受体。在凝胶迁移试验中，我们鉴定出在用熊果酸或齐墩果酸处理的F9细胞核蛋白中与糖皮质激素反应元件（GRE）结合的蛋白质因子。加入未标记的GRE寡核苷酸后，GRE结合蛋白的结合活性消失。综上所述，这些结果表明熊果酸和齐墩果酸可以诱导F9细胞分化，并可能通过与糖皮质激素受体或其类似核受体形成复合物来调节分化特异性基因的表达。
