Growth inhibition by progestins in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affinity binding site for R5020 (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PgR. 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 PgR. In contrast to the original cells, estrogen receptors could not be detected in IK-90 cells, and an addition of 17 beta-estradiol (10 nM) to culture medium failed to increase PgR. Accumulation of glycogen in cytoplasm of IK-90 cells in response to R5020 (0.1-1 microM) was observed by periodic acid-Schiff staining. The addition of R5020 to culture medium (0.1-1 microM) also caused a marked decrease in the growth of IK-90 cells, whereas the other steroids including 17 beta-estradiol, tamoxifen, testosterone, and cortisol had no significant effects. These results demonstrate for the first time the presence of a progestin-responsive human endometrial cancer cell line that contains estrogen-independent functional PgR. IK-90 cells appear to be an ideal model for studying the mechanism of the antiproliferative effect of progestin on endometrial cancer cells.