Prostate apoptosis in response to castration in wild-type and nerve growth factor-induced gene A-deficient mice

Objective: Nerve growth factor-induced gene A (NGFIA) is a transcription factor implicated in androgen deprivation-induced apoptosis in an androgen-sensitive prostate cell line (1,2). The objective of our study was to investigate the role of NGFIA in prostate apoptosis in response to androgen ablation in a mouse animal model lacking the gene. Materials and Methods: Wild-type mice (n = 56) and NGFIA-deficient mice ("knock-out") (n = 16) were surgically castrated. The animals were killed at 0 (noncastrated controls), 1, 3, 5, 7, 10, 14, and 21 days after castration, and the prostates were harvested. Tissue sections were stained for morphologic analysis and quantification of apoptosis using a terminal deoxynucleotidyl transferase biotinylated deoxyuridine triphosphate nick-end labeling (TUNEL) strategy. Apoptosis was quantitatively measured by counting the number of TUNEL-positive cells/100 epithelial cells by light microscopy. The percentage of apoptosis was compared for wild-type mice versus NGFIA-deficient mice after castration at the defined time points. Results: We found a statistically significant increase in the mean percentage of prostate cell apoptosis within 7-21 days after castration in both wild-type and NGFIA-deficient mice (p < 0.05). However, there was no statistically significant difference in the mean percentage of apoptotic prostate cells between wildtype and NGFIA-deficient mice 1-5 or 7-21 days after castration (p > 0.05). Conclusion: NGFIA does not seem to play a critical role in prostate apoptosis induced by androgen ablation in this mouse model.