CDK5 is a novel regulatory protein in PPARgamma ligand-induced antiproliferation.
Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclin-dependent kinase family and has been studied mainly in the differentiation of post-mitotic neurons. The purpose of this study was to determine the presence of cdk5 expression and activity in colon cancer cells and to investigate its role in the regulation of PPARgamma ligand-induced antiproliferation. We observed that cdk5 protein levels and kinase activity were elevated in both HT-29 cells and human tumor tissue in comparison to decreased levels in normal colonic mucosa. To elucidate cdk5's role in PPARgamma ligand-induced antiproliferation of colon cancer cells, HT-29 cells were treated with ciglitazone. A dose- and time-dependent decrease in cell proliferation were observed after ciglitazone exposure, which correlated with a decrease in cdk5 protein expression and kinase activity. Importantly, these ciglitazone-induced antiproliferative changes were reversed when cdk5 was overexpressed. Although present, p35, the regulatory protein of cdk5, showed no significant changes in protein expression with the introduction of ciglitazone. This is the first report of cdk5/p35 expression and kinase activity in colon cancer cells, which is associated with ciglitazone-induced antiproliferation in HT-29 cells.
Kim
Eugene
E
Division of Surgical Oncology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Chen
Fei
F
Wang
Chia-Chi
CC
Harrison
Lawrence E
LE
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis* / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D047495:PPAR gamma / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C039671:ciglitazone