Progesterone receptor A and B expression and progestagen treatment in growth and spread of endometrial cancer cells in nude mice

In endometrial cancer, decreased expression of progesterone receptor (PR) isotypes A and B (PRA and PRB) is a feature of poorly differentiated tumours. In distant metastases, PRB is the predominantly expressed isotype and endometrial cancer cells that express PRB have been observed to be more invasive. Furthermore, PRB-associated in vitro invasion is markedly inhibited by progestagens. In the present study, ovariectomized mice were injected intraperitoneally with Ishikawa endometrial cancer cells that express only PRA, only PRB, both PRA and PRB, or no PR. Half of the mice were substituted with medroxyprogesterone acetate (MPA). After ten weeks, growth and spread of the cancer cells were examined macroscopically, microscopically, and by PCR detection. Without MPA substitution, cells that express only PRB were found to be the most proliferative and migrative, while cells that express only PRA, both receptor isotypes, or no PR, showed minimal growth and spread. MPA appeared to inhibit growth and spread of PR-positive cells. Surprisingly, when mice that were inoculated with PR-negative cells were substituted with MPA, this resulted in massive abdominal tumour growth. These results provide further evidence that over-expression of PRB in endometrial cancer contributes to the development of a more aggressive phenotype. MPA inhibits tumour growth and spread of PR-positive cells, but can also have an indirectly stimulating effect on PR-negative tumour cells, probably through a host-mediated response.