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 volu me 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 induc ed a wave of apoptosis, whereas in the PC-EW tumor, necrotic cell deat h 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 rem ained, the major part of which was localized in the (murine) stromal c ompartment of the tumors. In contrast to the PC-EW tumors, regrowth of androgen-ablated PC-82 tumors was rapidly induced by androgen resubst itution. The differences in response of these tumor models to androgen depletion and repletion appear to be related to the putative involvem ent of different cell death pathways. The role of the stroma in these processes is unclear. (C) 1993 Wiley-Liss, Inc.