Circulating
insulin-like growth factor binding protein 1 (IGFBP1) levels vary in response to nutritional status, and pre-clinical studies suggest that elevated IGFBP1 may be protective against the development and progression of
prostate cancer. We hypothesized that global deletion of Igfbp1 would accelerate the development of
prostate cancer in a c-Myc transgenic mouse model. To test our hypothesis, c-Myc transgenic mice (Myc/BP-1 wild-type (WT)) were crossed and interbred with the Igfbp1 knockout mice (Myc/BP-1 KO). The animals were placed on a
high-protein diet at weaning, weighed every 2 weeks, and euthanized at 16 weeks of age. Prostate histopathology was assessed and proliferation status was determined by Ki-67 and
proliferating cell nuclear antigen analyses. IGF-related serum
biomarkers and body composition were measured. No significant difference in the incidence of
prostate cancer was observed between the Myc/BP-1 KO and the Myc/BP-1 WT mice (65 and 80% respectively, P=0.48). Proliferation was significantly decreased by 71% in prostate tissue of Myc/BP-1 KO mice compared with Myc/BP-1 WT mice. Myc/BP-1 KO mice exhibited a significant 6.7% increase in
body weight relative to the Myc/BP-1 WT mice that was attributed to an increase in fat mass. Fasting
insulin levels were higher in the Myc/BP-1 KO mice without any difference between the groups in fasting
glucose concentrations. Thus, contrary to our hypothesis, global deletion of Igfbp1 in a c-Myc transgenic mouse model did not accelerate the development of
prostate cancer. Global Igfbp1 deletion did result in a significant increase in
body weight and body fat mass. Further studies are required to understand the underlying mechanisms for these metabolic effects.