INDUCTION OF DIFFERENTIATION IN THE CULTURED F9 TERATOCARCINOMA STEM-CELLS BY TRITERPENE ACIDS

The effects of the triterpene acids, ursolic acid and oleanolic acid, on the differentiation of F9 teratocarcinoma stein cells were studied. These agents caused the morphological change of F9 cells into endoder m cells, as did retinoic acid (RA). Moreover, expression of laminin B1 , type IV collagen and retinoic acid receptor beta (RARbeta) increased in ursolic- and oleanolic-acid treated F9 cells. Since these agents a re structurally similar to the glucocorticoid hormone, we studied the effects of dexamethasone, a synthetic glucocorticoid, on F9 cells. Dex amethasone also induced the morphological change and altered the expre ssion of laminin B1, type IV collagen, and RARbeta in F9 cells. In add ition, transcription of glucocorticoid receptor was detected after tre atment with these three agents. According to Southwestern blot analysi s, a 94-kDa protein, thought to be a glucocorticoid receptor, was dete cted in F9 cells treated with these agents. In a gel-shift assay, we i dentified protein factors binding to the glucocorticoid-responsive ele ment (GRE) in the nuclear proteins from F9 cells treated with ursolic or oleanolic acid. The binding activity of the GRE-binding protein dis appeared on the addition of unlabeled GRE oligonucleotide. Taken toget her, these results suggest that UA and OA can induce the differentiati on of F9 cells and may regulate the expression of differentiation-spec ific genes, probably by forming a complex with the glucocorticoid rece ptor or its analogous nuclear receptor.