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.
Highlights
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”
The results presented in the recent report above have been extended to the human peripheral blood mononuclear cells (PBMCs).The objective of the new study described below was to investigate whether the expression of p27 in the human PBMCs might be inversely associated with potential carcinogenic risk in obese type 2 diabetic individuals relative to the lean normal controls
Available cryopreserved human PBMCs were used to investigate the expression of p27(Kip1) in human peripheral blood mononuclear cells (PBMCs) from obese type 2 diabetic and lean normal donors, Purchasing these cells did not require approval from the Institutional Review Board (IRB)(University of Alabama at Birmingham
Summary
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”. 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 be inversely associated with potential carcinogenic risk in obese type 2 diabetic individuals relative to the lean normal controls. (2014) 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. P27(Kip1) 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 rate of DNA replication in the S phase and the risk of developing cancer. As for the study of the expression of p27 in human breast cancer cells in vitro, various nutritional or chemopreventive anti-cancer agents, including retinoic acids, 4-hydroxitamoxifen, resveratrol, curcumin, and others, significantly increased the expression of p27 in these cells and, various nutritional pro-cancer agents, including glucose, insulin and branched-chain amino acids, significantly decreased the expression of p27 in these cells [12]-[14]
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