Intermittent food restriction prevents mammary tumors

间歇性食物限制可预防乳腺肿瘤

• 批准号: 6777829
• 负责人: Margot P Cleary
• 金额: $ 24.6万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6777829
• 关键词: apoptosis; biological signal transduction; breast neoplasms; caloric dietary content; cancer prevention; carcinogenesis; cell proliferation; dietary lipid; dietary restriction; disease /disorder etiology; disease /disorder model; gene expression; genetically modified animals; growth factor receptors; hormone receptor; insulinlike growth factor; laboratory mouse; leptin; longitudinal animal study; mouse mammary tumor virus; nutrition aspect of cancer; nutrition related tag

DESCRIPTION (provided by applicant): Many attempts have been made to identify dietary components that prevent development of breast cancer and/or mammary tumors (MTs). Few studies have produced conclusive findings. However, chronic caloric restriction consistently lowers MT incidence and extends latency in rodents. We find that intermittent restriction/refeeding prevents MT development in transgenic MMTV-TGF-a mice to a greater degree than does chronic restriction, i.e., 3% vs 44% incidence (vs 77% for ad libitum-fed mice). Thus, the manner in which calories are restricted has a major impact on MT development. Hypotheses: 1- The protective effect of intermittent restriction/refeeding is mediated by decreased serum IGF-I and leptin and effects on signaling pathways and/or proliferation/apoptosis; 2-The protective effect of intermittent restriction/refeeding is dependent upon periods of moderately severe caloric restriction and is modified by caloric intake and/or nutrient composition during refeeding; 3- The protective effects of chronic restriction and intermittent restriction/refeeding are dependent upon tumor etiology. In Specific Aim 1 the effect of intermittent restriction/refeeding and chronic restriction on serum IGF-I and leptin in longitudinal and cross-sectional protocols will be assessed. In Specific Aim 2 the effect of intermittent restriction/refeeding and chronic restriction on apoptosis, proliferation, and gene expression of IGF-I and leptin and their receptors in mammary tissue and MTs will be determined. In Specific Aim 3 the effect of serum leptin levels on the protective response of intermittent restriction/refeeding regimen on MT development will be determined. Specific Aim 4 will determine if the protective effect of intermittent caloric restriction/refeeding is dependent upon the MT oncogene and/or background strain of the transgenic mouse. Our long-term objectives are to establish nutrition intervention strategies applicable to humans and/or to provide insights leading to the development of chemopreventive agents to mimic this protective effect.

描述（由申请人提供）：已经进行了许多尝试来确定预防乳腺癌和/或乳腺肿瘤（MT）发展的饮食成分。很少有研究得出结论性的结论。然而，长期热量限制会持续降低啮齿动物的 MT 发生率并延长潜伏期。我们发现，间歇性限制/再喂养比长期限制更大程度地阻止转基因 MMTV-TGF-a 小鼠的 MT 发育，即，发生率分别为 3% 和 44%（随意喂养的小鼠为 77%）。因此，限制热量的方式对 MT 的发展有重大影响。假设： 1- 间歇性限制/重新喂养的保护作用是由血清 IGF-I 和瘦素减少以及对信号通路和/或增殖/凋亡的影响介导的； 2-间歇性限制/重新喂养的保护作用取决于中度严重热量限制的时期，并根据重新喂养期间的热量摄入和/或营养成分而改变； 3- 长期限制和间歇性限制/再喂养的保护作用取决于肿瘤病因。在具体目标 1 中，将评估纵向和横向方案中间歇性限制/再喂养和长期限制对血清 IGF-I 和瘦素的影响。在具体目标 2 中，将确定间歇性限制/再喂养和长期限制对乳腺组织和 MT 中 IGF-I 和瘦素及其受体的细胞凋亡、增殖和基因表达的影响。在具体目标 3 中，将确定血清瘦素水平对间歇性限制/再喂养方案对 MT 发育的保护反应的影响。具体目标 4 将确定间歇性热量限制/再喂养的保护作用是否取决于转基因小鼠的 MT 癌基因和/或背景品系。我们的长期目标是建立适用于人类的营养干预策略和/或提供有助于开发化学预防剂以模仿这种保护作用的见解。