Global Igfbp1 deletion does not affect prostate cancer development in a c-Myc transgenic mouse model.
Global Igfbp1 deletion does not affect prostate cancer development in a c-Myc transgenic mouse model.
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DOI：
10.1530/joe-11-0240
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Galet C
中科院分区：
文献类型：
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作者：
Gray A;Aronson WJ;Barnard RJ;Mehta H;Wan J;Said J;Cohen P;Galet C
循环中的IGFBP-1水平随营养状况而变化，临床前研究表明，升高的IGFBP-1可能对前列腺癌的发生和发展有保护作用。我们假设在c-Myc转基因小鼠模型中，IGFBP-1的全局缺失会加速前列腺癌的发展。为了验证我们的假设，我们将c-Myc转基因小鼠（Myc/BP-1 WT）与IGFBP-1敲除小鼠（Myc/BP-1 KO）杂交。这些动物在断奶时被喂食高蛋白饮食，每两周称重一次，并在16周龄时被安乐死。通过Ki - 67和PCNA分析评估前列腺组织病理学和增殖情况。测量igf相关的血清生物标志物和体成分。Myc/BP-1 KO与Myc/BP-1 WT小鼠前列腺癌发生率无显著差异（分别为65%和80%，p= 0.48）。与Myc/BP-1 WT小鼠相比，Myc/BP-1 KO小鼠前列腺组织的增殖明显减少71%。由于脂肪量增加，Myc/BP-1 KO小鼠的体重相对于Myc/BP-1 WT小鼠显著增加6.7%。Myc/BP-1 KO小鼠的空腹胰岛素水平较高，各组之间的空腹血糖浓度没有任何差异。因此，与我们的假设相反，在c-Myc转基因小鼠模型中，IGFBP-1的全局缺失并没有加速前列腺癌的发展。IGFBP-1的缺失确实会导致体重和体脂量的显著增加。需要进一步的研究来了解这些代谢作用的潜在机制。
Circulating IGFBP-1 levels vary in response to nutritional status, and preclinical studies suggest that elevated IGFBP-1 may be protective against the development and progression of prostate cancer. We hypothesized that global deletion of IGFBP-1 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 WT) were crossed and interbred with the IGFBP-1 knockout mice (Myc/BP-1 KO). The animals were placed on a high protein diet at weaning, weighed every two weeks, and euthanized at 16 weeks of age. Prostate histopathology was assessed and proliferation status was determined by Ki 67 and PCNA 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 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 to 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 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 IGFBP-1 in a c-Myc transgenic mouse model did not accelerate the development of prostate cancer. Global IGFBP-1 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.