title: Overexpression of cdk4/cyclin D1 induces apoptosis in PC12 cells in the presence of trophic support.
abstract: The induction of apoptosis by cell cycle regulator molecules under conditions optimal for exponential growth was examined in rat pheochromocytoma PC12 cells by overexpression of cyclins and cyclin-dependent kinases (cdks). By flow cytometry and by immunofluorescence, only cells overexpressing cdk4 or cyclin D1 underwent apoptosis, which was not associated with G1-arrest. Cdk4 kinase activity was significantly higher in cdk4-, or cyclin D1-expressing cells. Furthermore, induction of apoptosis by cdk4 was abrogated by co-transfection of p16(INK4), or dominant negative cdk4. These results suggest that upregulation of cdk4 kinase activity is a primary and critical mediator of apoptosis in PC12 cells under physiological conditions.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Dobashi
authors.forename: M
authors.initials: M
authors.lastname: Kitagawa
authors.forename: S
authors.initials: S
authors.lastname: Kamekura
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Kadoya
authors.forename: T
authors.initials: T
authors.lastname: Kameya
mesh_terms: D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D048429:Cell Size; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D016193:G1 Phase; D015870:Gene Expression; D005799:Genes, Dominant; D009154:Mutation; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins; D051381:Rats; D013997:Time Factors
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine; D016650:Fluorescein-5-isothiocyanate