Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer.
Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer.
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DOI：
10.1249/mss.0b013e31819f1f05
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发表时间：
2009-08
影响因子：
4.1
通讯作者：
Hursting SD
中科院分区：
文献类型：
--
作者：
Colbert LH;Westerlind KC;Perkins SN;Haines DC;Berrigan D;Donehower LA;Fuchs-Young R;Hursting SD
身体活跃的女性患乳腺癌的风险降低，但所需的活动剂量以及能量平衡和其他潜在机制的作用尚未在动物模型中充分探索。我们在p53缺陷（p53+/−）：MMTV-Wnt-1转基因小鼠中研究了跑步机和轮跑对乳腺肿瘤发生和生物标志物的影响。在实验1中，将雌性小鼠（9周龄）随机分配到以下组：跑步机运动5 d/wk，45 min/d，5%等级，20 m/min，~0.90 km/d（TREX 1，n=20）; 24 m/min，~1.08 km/d（TREX 2，n=21）;或非运动对照（CON-TREX，n=22）。在实验2中，小鼠被随机分配到自愿轮跑（WHL，n=21，2.46 ± 1.11 km/d（平均值± SD））或非运动对照（CON-WHL，n=22）。在约9周时测量身体组成，在研究约9周开始的2-3个月时间点测量血清胰岛素样生长因子-1（IGF-1）。当肿瘤达到1.5cm、小鼠变得濒死或每个处理组仅剩下一只小鼠时，处死小鼠。TREX 1（24周）和TREX 2（21周）的存活中位存活时间短于CON-TREX（34周; p<0.01）; WHL和CON-WHL存活相似（23 vs. 24周; p=0.32）。与CON-TREX相比，TREX 2增加了乳腺癌的多样性; WHL的肿瘤发生率高于CON-WHL。所有运动的动物都比它们各自的对照组轻，并且WHL比CON-WHL具有更低的体脂（p<0.01）。IGF-1在两组间差异无统计学意义（p>0.05）。尽管对体重、体脂或IGF-1有益或无影响，但在这种自发性乳腺癌p53缺陷小鼠模型中，运动对肿瘤发生有不利影响。
Physically active women have a reduced risk of breast cancer, but the dose of activity necessary and the role of energy balance and other potential mechanisms have not been fully explored in animal models. We examined treadmill and wheel running effects on mammary tumorigenesis and biomarkers in p53-deficient (p53+/−): MMTV-Wnt-1 transgenic mice. Female mice (9 wks old) were randomly assigned to the following groups in Experiment 1: treadmill exercise 5 d/wk, 45 min/d, 5% grade at 20 m/min, ~0.90 km/d (TREX1, n=20); at 24 m/min, ~1.08 km/d (TREX2, n=21); or a non-exercise control (CON-TREX, n=22). In Experiment 2, mice were randomly assigned to voluntary wheel-running (WHL, n=21, 2.46 ± 1.11 km/d (mean ± SD)) or a non-exercise control (CON-WHL, n=22). Body composition was measured at ~9 weeks and serum insulin-like growth factor-1 (IGF-1) at 2–3 monthly time points beginning at ~9 weeks on study. Mice were sacrificed when tumors reached 1.5 cm, mice became moribund, or there was only one mouse per treatment group remaining. TREX1 (24 wks) and TREX2 (21 wks) had shorter survival median survival times than CON-TREX (34 wks; p<0.01); WHL and CON-WHL survival was similar (23 vs. 24 wks; p=0.32). TREX2 had increased multiplicity of mammary gland carcinomas compared to CON-TREX; WHL had a higher tumor incidence than CON-WHL. All exercising animals were lighter than their respective controls, and WHL had lower body fat than CON-WHL (p<0.01). There was no difference in IGF-1 between groups (p>0.05). Despite beneficial or no effects on body weight, body fat, or IGF-1, exercise had detrimental effects on tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer.