Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells

BACKGROUND: It has been reported that p38 and c-jun operateas mediators of cell proliferation and differentiation. Therefore,by studying the roles of c-jun and p38 in the proliferationand differentiation of normal human endometrial cells, we canbetter understand the mechanism of these processes in endometrialcells. METHODS: Separation of glandular and stromal componentswas based on a modification of the work of Satyaswaroop et al.To confirm the purification of the endometrial cells and theexpression of the transfected SV40 large T antigen, immunocytochemicalanalysis and western blot analysis were performed. RESULTS:There were polygonal shapes in the stromal cells in the earlypassage 1–2, while the aged endometrial stromal cellswere spindle shaped. To investigate passage-dependent molecularevents in endometrial cells, the c-jun and pp38 levels wereexamined. Both c-jun and pp38 were significantly reduced withcellular aging and passages. To understand the role of c-jun,endometrial stromal cells were treated with SP600125 which isa specific inhibitor of c-jun. SP600125 induced morphologicalchanges of young endometrial stromal cells with polygonal shape;the young cells appeared as aged endometrial cells with spindleshape. In addition, an immortalized endometrial cell line wasestablished and shown to express activated c-jun, similiar tonormal endometrial cells. CONCLUSIONS: These results suggestthat the modulation of p38 and c-jun may play an important rolein the differentiation and proliferation of human endometrialcells.