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
Introduction. 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. Objective. 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. Methods. 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 invitro,
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. Results and Conclusion. 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 translation initiation activity of the p27Kip1 mRNA.
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