Higher Concentrations of Glucose or Insulin Increase the Risk of Various Types of Cancer in Obesity or Type 2 Diabetes by Decreasing the Expression of p27Kip1, a Cell Cycle Repressor Protein

摘要

Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.