TITLE:
Expression of p27(Kip1), a Cyclin-Dependent Kinase Inhibitor, in Human Peripheral Blood Mononuclear Cells Is Inversely Associated with Potential Carcinogenic Risk in Obese Type 2 Diabetic Individuals Relative to Lean Normal Controls
AUTHORS:
Isao Eto
KEYWORDS:
Zucker Rats, Liver, Kidney, Diabetic Nephropathy, 4E-BP1, MNK1, eIF4E
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.4 No.3,
July
16,
2014
ABSTRACT:
Introduction: The consensus report issued
jointly by the American Diabetes Association and the American Cancer Society
stated that “type 2 diabetes and cancer share many risk factors, but potential
biologic links between the two diseases are incompletely understood”. Interestingly,
however, a recent report suggested that the expression of p27(Kip1), a cell
cycle repressor protein, in the rodent liver was inversely associated with
potential carcinogenic risk in the genetic
rodent models of diabetic obesity. p27 is a cyclin-dependent kinase
inhibitor that, when down-regulated, allows the progression of the cell cycle
from G1 to S phase, thereby increasing the risk of developing cancer. Objective:
The objective of the study described below was to extend the results of the
recent report on the expression of p27 in the livers of obese, diabetic rodents
to the humans and investigate whether the expression of p27 in the human
peripheral blood mononuclear cells (PBMCs)
might also be inversely associated with potential carcinogenic risk in obese
type 2 diabetic individuals relative to the lean normal controls. Methods: Western immunoblot analysis was
performed to evaluate the expression of p27 and the two most relevant upstream
molecular signaling pathways of the expression of p27, namely 4E-BP1 and MNK1,
in human PBMCs obtained from obese type 2
diabetic individuals relative to the lean normal controls. Results: First, expression
of p27 in human PBMCs was significantly down-regulated in obese type 2 diabetic
individuals relative to the lean normal controls. Secondly, expression of p27
in human PBMCs was also significantly down-regulated in obese type 2 diabetic
African Americans relative even to the obese type 2 diabetic Caucasian
Americans. Conclusions: Expression of p27 in human PBMCs was inversely
associated with potential carcinogenic risk in obese type 2 diabetes relative
to the lean normal controls.