Involvement of Cell Cycle Regulators in Steroid Hormone-Induced Growth of Endometrial Carcinoma

The involvement of cell cycle regulators in steroid hormone-dependent growth and growth suppression was examined using cultured normal endometrial glandular cells and estrogen receptor (ER)/pregesterone receptor (PR)-positive endometrial carcinoma Ishikawa cells. The results indicated that the estradiol (E2)-induced upregulation of cydin Dl may play a crucial role in the growth of normal endometrial glandular cells and is mediated by c-Jun via an activating protein (AP)-1-binding site-like sequence of the promoter. However, in ER-positive Ishikawa cells, its molecular mechanism is different from the normal counterpart. In progestininduced growth suppression, accumulation of p27 protein plays an essential role in both normal and malignant endometrial cells, possibly via inhibition of the ubiquitin pathway of p27 degradation.