Basic Science| Volume 62, ISSUE 6, P873-887, June 2013

Expression of p27Kip1, a cell cycle repressor protein, is inversely associated with potential carcinogenic risk in the genetic rodent models of obesity and long-lived Ames dwarf mice

  • Isao Eto
    Tel.: +1 205 934 4099; fax: +1 205 934 7049.
    Department of Nutrition Sciences, University of Alabama at Birmingham, 316 Susan Mott Webb Nutrition Sciences Building, 1675 University Boulevard, Birmingham, AL 35294, USA
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Published:January 28, 2013DOI:



      The association of genetic rodent models of obesity and cancer still remains a controversial issue. Although this controversy has largely been resolved in recent years for homozygous leptin receptor-deficient obese Zucker rats and homozygous long-lived Ames dwarf mice, it is still unresolved for homozygous leptin-deficient obese ob/ob mice.


      The objective of the present study described below was to investigate whether the expression of the cell cycle repressor protein p27(Kip1) is (a) down-regulated in the tumor-free homozygous leptin receptor-deficient obese Zucker rats as well as tumor-free homozygous leptin-deficient obese ob/ob mice and (b) up-regulated in the tumor-free homozygous long-lived Ames dwarf mice.


      To achieve this objective, we first performed western immunoblot analysis of the hepatic expression of p27. We then performed western immunoblot analysis and proteomic analysis of the hepatic expression of the proteins involved in the upstream molecular signaling pathways for the expression of p27. Lastly, we analyzed the serum levels of glucose, insulin, and branched-chain amino acids, all of which have been shown to regulate, causally and inversely, the expression of p27.


      The results indicated that the hepatic expression of p27 was down-regulated in the homozygous leptin receptor-deficient obese Zucker rats and up-regulated in the homozygous long-lived Ames dwarf mice as expected. We also found that the hepatic expression of p27 was down-regulated in the homozygous leptin-deficient obese ob/ob mice. This last observation was not completely consistent with all of the results of the published studies where homozygous leptin-deficient obese ob/ob mice were used.


      4E-BP1 (eukaryotic translation initiation factor 4E binding protein 1), AICAR (5-amino-4-imidazolecarboxamide riboside), AMPK (5′-AMP-activated protein kinase), CDI (cyclin-dependent kinase inhibitor), CDK (cyclin-dependent kinase), ERK (ERK MAP kinase), GAPDH (glyceraldehydes phosphate dehydrogenase), H & E staining (hematoxylin and eosin staining), MALDI (matrix-assisted laser desorption/ionization), MAPK (mitogen-activated protein kinase), MEK (mitogen-activated protein (MAP) kinase kinase), MNK (MAP kinase interacting kinase), MNU (N-methyl-N-nitrosourea), MS (mass spectrometry), mTOR (mammalian target of rapamycin), nano LC-MS/MS (nano liquid chromatography–tandem mass spectrometry), p21 (p21Cip1/Waf1), p27 (p27Kip1), PI3K (phosphoinositide 3-kinase), PKB (protein kinase B), RTK (receptor tyrosine kinase), S6K (p70 S6 kinase), TOF (time-of-flight), TSC (tuberous sclerosis complex)


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