Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model

It was previously shown in the PC-295 xenograft that the number of chromogranin A (CgA)-positive neu-roendocrine (NE) cells increased after androgen with-drawal. NE cells did not proliferate and differentiated from G0-phase-arrested cells. Here we further charac-terized NE differentiation, androgen receptor status, and apoptosis-associated Bcl-2 expression in the PC-295 model after androgen withdrawal to assess the origin of NE cells. PC-295 tumor volumes decreased by 50 % in 4 days. Intraperitoneal bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%, and the apoptosis was maximal at day 4. Andro-gen receptor expression and prostate-specific antigen (PSA) serum levels decreased rapidly within 2 days. The number of NE cells increased 6-fold at day 4 an