Progesterone receptors in endometrial cancer invasion and metastasis: development of a mouse model

Progestagens inhibit growth of endometrial cancer cells in vivo and in vitro, and also are reported to inhibit endometrial cancer cell invasion. The progesterone receptor (PR) isotypes PRA and PRB have different transcriptional activity. There are indications that relative over expression of PRB could lead to development of a more invasive phenotype in endometrial cancer. To study the effect of progestagens and the two PR isotypes on tumor dissemination, in vitro and in vivo models should be applied. The Ishikawa endometrial cancer cell line (clone 3H12) was transfected to stably express a high level of human PRB (hPRB), which resulted in the PRB-1 sub-cell line. Ovariectomized athymic NMRI nu/nu mice were injected intraperitoneally with these PRB-1 cells. After 3, 5 and 10 weeks, the animals were sacrificed. Spread of PRB-1 cells in and outside the peritoneal cavity was studied macroscopically and microscopically, and also by PCR detection. After 10 weeks, the PRB-1 cells had formed extensive tumor mass in the peritoneal cavity. Also, cells could be detected outside the peritoneal cavity, indicating metastatic ability of these cells. The present study describes an in vivo model that can provide a valuable tool in studying the influence of progestagens and the two PR isotypes on endometrial cancer cell invasion and metastasis.