Estrogen treatment postpones the castration-induced dedifferentiation of Dunning R3327-PAP prostatic adenocarcinoma.
Male Copenhagen x Fisher F1 rats, transplanted with the androgen-sensitive Dunning R3327 PAP rat prostatic adenocarcinoma, were castrated when tumor volumes were approximately 1300 mm3. The rats were thereafter followed with measurements of tumor volume. Castration stopped tumor growth, but some of the tumors started to regrow after 7-36 weeks. These tumors relapsing from castration treatment were now considered to be androgen-insensitive. In this study, we defined relapse as the time when the tumor volume had increased to 200% of the volume at the time for castration. At this time, the rats were treated either with estradiol-17 beta (E2, 50 micrograms s.c. daily) or vehicle for 8 weeks. After this period, tumor morphology was examined. The tumors in the vehicle-treated group were heterogeneous, and both highly and more dedifferentiated parts were present. The tumor growth rate was correlated to the epithelial cell nuclear size and its variance, and to the mitotic index. In the E2-treated group, tumor growth rate was retarded throughout the treatment period, and dedifferentiated tumor areas were rare. Estrogen treatment resulted in a reduction of nuclear area and mitotic index, a changed nuclear shape, and an increased apoptotic index compared to that in vehicle-treated tumors. By castration, it is possible to induce an alteration of the androgen-sensitive Dunning R3327 PAP tumor phenotype to an androgen-insensitive tumor with an altered morphology. Estradiol-17 beta apparently inhibits not only the growth, but also postpones the castration-induced dedifferentiation of the tumor.
Department of Pathology, University of Umeå, Sweden.
M
M
Landström
J E
JE
Damber
A
A
Bergh
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004958:Estradiol / Q000627:therapeutic use*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011897:Random Allocation; D051381:Rats
D004958:Estradiol