[Growth inhibition by progestins in human endometrial cancer cells with progesterone receptors].
The presence of estrogen-independent progesterone receptors (PR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells. Scatchard plot analysis of cytoplasmic binding data in a subline (IK-90) revealed a high affinity binding site for promegestone (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PR. By low-salt sucrose gradient centrifugation, radioactive 8S and 4S peaks were found. The addition of 1 microM progesterone in culture medium resulted in a rapid nuclear translocation of cytoplasmic PR. Accumulation of glycogen in cytoplasm of the cells in response to 0.1 microM promegestone was observed by periodic acid-Schiff staining. Addition of various concentrations (1 nM-1 microM) of promegestone reduced the cell growth in a dose-dependent manner. The growth inhibition by promegestone was totally prevented by the concomitant addition of equimolar RU 486, a progestin antagonist. The other steroids including tamoxifen, cortisol, and testosterone had no significant effects on the growth of the cells. The growth-inhibitory effect of progestin on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy was also investigated. Addition of medroxyprogesterone acetate (1 nM-1 microM) caused a marked decrease in [3H]thymidine incorporation in cultured cancer cells from tumors with PR. From the viewpoint obtained in the present studies using both IK-90 cells and endometrial cancer cells in primary culture, it can be concluded that progestins produce regression of endometrial cancer directly via the PR system.
Tanizawa
O
O
Dept. of Obstetrics and Gynecology, Osaka University Medical School.
Terakawa
N
N
D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008525:Medroxyprogesterone / Q000378:metabolism / Q000494:pharmacology; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D045167:Progesterone Congeners / Q000378:metabolism / Q000494:pharmacology*; D011397:Promegestone / Q000378:metabolism / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014594:Uterine Neoplasms / Q000473:pathology*
D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D011397:Promegestone; D008525:Medroxyprogesterone