Changes in tumor characteristics during progression of the R3327 HI experimental prostatic carcinoma

The R3327 HI experimental prostatic carcinoma was serially transplanted through six generations of castrated host rats to examine changes in the capacity to synthesize progesterone receptor (PgR) in response to diethylstilbestrol (DES) stimulation during progression from a well-differentiated state containing a significant stromal component to a poorly differentiated state with virtually no stroma. During progression, changes in growth rate and histopathology occurred in stepwise fashion, the most marked changes being observed between the first and second and between the fourth and fifth generations. The capacity for PgR synthesis in response to DES treatment fell progressively, but did not reach statistical significance during the first four generations. By the sixth generation, the stromal component had virtually disappeared, and no estrogen receptor (ER) or PgR was detectable. During the course of the investigation, a monoclonal antibody that reacts with rat PgR became available, and immunohistochemistry with this antibody confirmed that DES-induced PgR was present in stromal cells. We conclude that this work supports the hypothesis that prostatic stroma is a target tissue for estrogen and that this model may be useful for the investigation of other events associated with progression.