title: Enhanced cytotoxicity of 5-FU by bFGF through up-regulation of uridine phosphorylase 1.
abstract: Anti cancer agent 5-FU (Fluoro Uracil) is a prodrug that can be metabolized and then activated to interfere with RNA and DNA homeostasis. However, the majority of administered 5-FU is known to be catabolized in vivo in the liver where Dihydropyrimidine dehydrogenase (DPD) is abundantly expressed to degrade 5-FU. The biological factors that correlate with the response to 5-FU-based chemotherapy have been proposed to include uridine phosphorylase (UPP), thymidine phosphorylase (TPP), p53 and microsatellite instability. Among these, the expression of UPP is known to be controlled by cytokines such as TNF-alpha, IL1 and IFN-gamma. Our preliminary study using a DNA microarray technique showed that basic fibroblast growth factor (bFGF) markedly induced the expression of UPP1 at the transcription level. In the present study, we investigated whether bFGF could modulate the expression of UPP1 in osteo-lineage cells and examined the sensitivity of these cells to 5-FU mediated apoptosis.
authors.affiliation: Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju, 361-763, Korea.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Im
authors.forename: Hea Kyeong
authors.initials: HK
authors.lastname: Shin
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kim
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Seung-Ryul
authors.initials: SR
authors.lastname: Kim
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D014543:Uridine Phosphorylase / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D016222:Fibroblast Growth Factor 2; D014543:Uridine Phosphorylase; D005472:Fluorouracil