Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Nutr Cancer. 2011;63(3):389-401. doi: 10.1080/01635581.2011.535968.
Chronic calorie restriction (CCR) prevents mammary tumor (MT) development in rodents. We reported that intermittent calorie restriction (ICR) provides greater protection than CCR in MMTV-TGF-α mice. The mammalian target of rapamycin (mTOR) pathway is involved in MT development. Here the impact of ICR versus CCR on proteins associated with mTOR signaling in mammary tissues and MTs from MMTV-TGF-α mice was determined. Mice were enrolled at 10 wk of age into ad libitum-fed (AL), CCR, and ICR groups and followed until 37/38 or 73/74 wk of age. Time points 37 and 73 followed 3 wk of 50% restriction for ICR mice, while 38 and 74 followed 1 wk of refeeding of ICR mice. Calorie restriction reduced serum IGF-I levels except for older CCR mice. At 37/38 wk, calorie restriction decreased mTOR, p70S6K, HIF-1, EGFR, and Erk protein activation and increased p4EBP1 and VEGF in mammary fat pads. At 73/74 wk, both modes of calorie restriction lowered IGF-I protein expression levels and Akt activation in MTs and mammary fat pads, and CCR increased mTOR, p70S6K, p4EBP1, and HIF-1 expression. ICR had inconsistent effects on these proteins in older mice. These results indicate that mTOR signaling proteins are modulated by age and type of calorie restriction.
慢性热量限制（CCR）可预防啮齿动物的乳腺肿瘤（MT）发展。我们报道间歇热量限制（ICR）比 MMTV-TGF-α 小鼠中的 CCR 提供更大的保护作用。哺乳动物雷帕霉素靶蛋白（mTOR）途径参与 MT 的发展。在此，确定了 ICR 与 CCR 对乳腺组织和 MMTV-TGF-α 小鼠 MT 中与 mTOR 信号相关的蛋白质的影响。将小鼠在 10 周龄时纳入自由喂养（AL）、CCR 和 ICR 组，并一直随访至 37/38 或 73/74 周龄。ICR 小鼠的时间点 37 和 73 分别在限制 50%热量的 3 周后进行，而 38 和 74 则在 ICR 小鼠重新喂食 1 周后进行。热量限制降低了血清 IGF-I 水平，除了老年 CCR 小鼠。在 37/38 周时，热量限制降低了 mTOR、p70S6K、HIF-1、EGFR 和 Erk 蛋白的激活，并增加了乳腺脂肪垫中的 p4EBP1 和 VEGF。在 73/74 周时，两种热量限制方式均降低了 IGF-I 蛋白在 MT 和乳腺脂肪垫中的表达水平以及 Akt 的激活，而 CCR 增加了 mTOR、p70S6K、p4EBP1 和 HIF-1 的表达。ICR 在老年小鼠中对这些蛋白质的影响不一致。这些结果表明，mTOR 信号蛋白受年龄和热量限制类型的调节。
