Castration-induced changes in morphology, androgen levels, and proliferative activity of human prostate cancer tissue grown in athymic nude mice.
The transplantable human prostate tumor lines PC-82 and PC-EW regress after androgen depletion. The castration-induced decline in tumor volume was faster in the PC-EW tumor (half-life 6 days) than in the PC-82 tumor (half-life 18 days), despite similar castrate androgen levels of less than 3 pmol/g tissue. Androgen ablation of the PC-82 tumor induced a wave of apoptosis, whereas in the PC-EW tumor, necrotic cell death was predominantly observed. The proliferative activity (BrdU index) of PC-82 and PC-EW tumor tissue declined from 3% to less than 1% after castration. After androgen depletion, some proliferative activity remained, the major part of which was localized in the (murine) stromal compartment of the tumors. In contrast to the PC-EW tumors, regrowth of androgen-ablated PC-82 tumors was rapidly induced by androgen resubstitution. The differences in response of these tumor models to androgen depletion and repletion appear to be related to the putative involvement of different cell death pathways. The role of the stroma in these processes is unclear.
Department of Urology, Erasmus University, Rotterdam, The Netherlands.
W M
WM
van Weerden
A
A
van Kreuningen
N M
NM
Elissen
M
M
Vermeij
F H
FH
de Jong
G J
GJ
van Steenbrugge
F H
FH
Schröder
D000818:Animals; D013196:Dihydrotestosterone / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D013196:Dihydrotestosterone; D013739:Testosterone