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Castration-Induced Apoptosis in the Rat Ventral Prostate Is Associated with Increased Expression of Genes Encoding Insulin-Like Growth Factor Binding Proteins 2, 3, 4 and 5

Lady Davis Research Institute of the Jewish General Hospital and Departments of Medicine (T.N., M.P., H.H.), Oncology (M.P.) and Urology (H.H.), McGill University, Montréal, Québec, Canada H3T 1E2

Address all correspondence and requests for reprints to: Dr. Hung Huynh, McGill University, Lady Davis Research Institute of the Jewish General Hospital, Department of Medicine, Montréal, Québec H3T 1E2, Canada.

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 labeling 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.

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