Lower Concentrations of Glucose or Insulin Decrease the Risk of Various Types of Cancer in the Long-Lived Ames Dwarf Mouse by Increasing the Expression of p27Kip1, a Cell-Cycle Repressor Protein

• 作者: Isao Eto
• 来源期刊: 美国分子生物学期刊(英文)
• 学科: 医学
• 关键词: Cancer GLUCOSE Insulin Caloric Restriction Long-Lived Ames Dwarf Mouse P27KIP1 Cell-Cycle Repressor Protein
• 年，卷（期）: 2020,（3）
• 页码范围: 148-164
• 页数: 17页
• 分类号: R73

摘要

<strong>Introduction</strong>.<span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> The molecular biological mechanism of the increased incidence of the various types of cancer in obesity or type 2 diabetes in rodents or humans has largely been resolved in recent years. By contrast, the molecular biological mechanism of the decreased, not increased, incidence of the various types of cancer in the homozygous long-lived Ames dwarf mice still remains unresolved. </span><b><span style="font-family:Verdana;">Objective.</span></b><span style="font-family:Verdana;"> The first objective of the present study was to investigate whether the decrease in the incidence of cancer in the homozygous long-lived Ames dwarf mice is due to the increase, not decrease, in the expression of p27Kip1, a cell cycle repressor protein. The second objective was to investigate whether the decrease in the incidence of cancer in the homozygous long-lived Ames dwarf mice is due to the decrease, not increase, in the levels of glucose or insulin. </span><b><span style="font-family:Verdana;">Methods.</span></b><span style="font-family:Verdana;"> To achieve these objectives, we first performed western immunoblot analysis of the hepatic expression of p27Kip1 protein. We then performed, using a human breast cancer cell line </span><i><span style="font-family:Verdana;">in</span></i> <i><span style="font-family:Verdana;">vitro</span></i><span style="font-family:Verdana;">, the luciferase reporter plasmid assay to determine whether the translation initiation activity of the p27Kip1 mRNA is increased when the concentrations of either glucose or insulin are decreased. </span><b><span style="font-family:Verdana;">Results and Conclusion. </span></b><span style="font-family:Verdana;">The results of the first objective indicated that the hepatic expression of p27Kip1 protein was up-regulated in the homozygous long-lived Ames dwarf mice as expected. We also found that the lower concentrations of glucose or insulin increased the transla