title: Global Igfbp1 deletion does not affect prostate cancer development in a c-Myc transgenic mouse model.
abstract: 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.
authors: Department of Integrative Biology and Physiology, University of California at Los Angeles, Los Angeles, California, USA.
authors: Ashley
authors: A
authors: Gray
authors: William J
authors: WJ
authors: Aronson
authors: R James
authors: RJ
authors: Barnard
authors: Hemal
authors: H
authors: Mehta
authors: Junxiang
authors: J
authors: Wan
authors: Jonathan
authors: J
authors: Said
authors: Pinchas
authors: P
authors: Cohen
authors: Colette
authors: C
authors: Galet
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D017353:Gene Deletion; D016259:Genes, myc; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1