title: Role of p16(INK4a) in the inhibition of DNA synthesis stimulated by HGF or EGF in primary cultured rat hepatocytes.
abstract: In the present study, we investigated the role of p16(INK4a) in the inhibition of DNA synthesis stimulated by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) using RNA interference in primary cultured rat hepatocytes. The transfection of small interfering RNAs targeting p16(INK4a) reduced the corresponding mRNA and protein expression by more than approximately 90% and 50%, respectively, at 24 h after transfection. In the cells transfected with p16(INK4a) small interfering RNA, control, HGF, and EGF-stimulated DNA synthesis as assessed by (3)H-thymidine incorporation increased by approximately 1.5-fold, 1.6-fold, and 1.7-fold, respectively, compared with that in the control small interfering RNA-transfected cells. These findings indicate that p16(INK4a) plays a significant role in the inhibition of DNA synthesis.
authors.affiliation: Department of Nutrition and Physiology, Nihon University College of Bioresource Sciences, Kameino Fujisawa 252-8510, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Harashima
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
authors.forename: Shingo
authors.initials: S
authors.lastname: Niimi
mesh_terms: D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor