Nickerson T, Pollak M, Huynh H
Lady Davis Research Institute of the Jewish General Hospital and Department of Medicine, McGill University, Montreal, Quebec, Canada.
Endocrinology. 1998 Feb;139(2):807-10. doi: 10.1210/endo.139.2.5912.
Insulin-like growth factor binding proteins (IGFBPs) have recently been demonstrated to act as regulators of apoptosis in vitro in both prostate and breast cancer cell lines. We show here that gene expression of IGFBP-2,-3,-4 and -5 increase rapidly in the rat ventral prostate following castration. Increases in IGFBP mRNA levels were detectable by Northern blotting by 6 hours and reached 5 to 10 fold of control levels at 72 hours after castration. Apoptosis in the ventral prostate, as detected in situ by the TUNEL method, was also induced as early as 6 hours after castration. TRPM-2/clusterin, a gene known to be associated with involution of the prostate, was not detected in sham castrated controls but was expressed by 24 hours following androgen ablation. IGF-I mRNA levels increased to 160% of control values within 6 hours following castration, then decreased gradually over the next 72 hours to 35% of control. Affinity labelling experiments demonstrated that IGF-I receptor levels increased initially after castration with peak binding at 24 hours, then declined to levels lower than control. These results suggest that rapid induction of IGFBPs in the rat ventral prostate following androgen ablation may play a role in apoptosis and involution of the prostate gland.
胰岛素样生长因子结合蛋白（IGFBPs）最近已被证明在体外对前列腺和乳腺癌细胞系中的细胞凋亡具有调节作用。我们在此表明，去势后大鼠腹侧前列腺中IGFBP-2、-3、-4和-5的基因表达迅速增加。通过Northern印迹法在去势后6小时即可检测到IGFBP mRNA水平的升高，在去势后72小时达到对照水平的5至10倍。通过TUNEL法原位检测，腹侧前列腺中的细胞凋亡也早在去势后6小时就被诱导。TRPM-2/聚集素是一种已知与前列腺退化相关的基因，在假去势对照中未检测到，但在雄激素去除后24小时表达。去势后6小时内，IGF-I mRNA水平增加到对照值的160%，然后在接下来的72小时内逐渐下降至对照的35%。亲和标记实验表明，去势后IGF-I受体水平最初升高，在24小时达到结合峰值，然后下降至低于对照的水平。这些结果表明，雄激素去除后大鼠腹侧前列腺中IGFBPs的快速诱导可能在前列腺的细胞凋亡和退化中起作用。
