Prostate Apoptosis in Response to Castration in Wild‐Type and Nerve Growth Factor‐Induced Gene A‐Deficient Mice

C. Naughton, W. Tourtellotte, Deborah S. Smith, J. Milbrandt
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Abstract

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). Conclusion: NGFIA does not seem to play a critical role in prostate apoptosis induced by androgen ablation in this mouse model.
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野生型和神经生长因子诱导的基因A缺陷小鼠对去势的前列腺凋亡反应
目的:神经生长因子诱导基因A (NGFIA)是一种在雄激素敏感的前列腺细胞系中参与雄激素剥夺诱导的细胞凋亡的转录因子(1,2)。我们的研究目的是在缺乏该基因的小鼠动物模型中研究NGFIA在雄激素消融后前列腺细胞凋亡中的作用。材料与方法:采用手术阉割野生型小鼠(n = 56)和ngfia缺失小鼠(“敲除”)(n = 16)。分别于去势后0、1、3、5、7、10、14、21天处死,取前列腺。采用末端脱氧核苷酸转移酶生物素化脱氧尿苷三磷酸镍端标记(TUNEL)策略对组织切片进行形态学分析和细胞凋亡定量。光镜下计数tunel阳性细胞数/100上皮细胞数,定量测定细胞凋亡。在规定的时间点,比较野生型小鼠和ngfia缺陷小鼠去势后的细胞凋亡百分比。结果:野生型和ngfia缺失小鼠去雄后7 ~ 21天前列腺细胞凋亡的平均百分比均有统计学意义(p < 0.05)。结论:NGFIA在雄激素消融术诱导的前列腺细胞凋亡中似乎不起关键作用。
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