title: KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines.
abstract: BACKGROUND
  We previously investigated the mRNA expression of colorectal cancer cell lines via a microarray analysis and found several genes that were significantly up-regulated by oncogenic KRAS under serum-starved conditions. Of these genes, we focused on ribonucleotide reductase M2 (RRM2), which was reported to be associated with DNA synthesis.
  
  
  METHODS
  Cell proliferation and colony formation assays were performed using HCT116 cells transfected with lentiviral RRM2-shRNAs.
  
  
  RESULTS
  Under serum-starved conditions, the expression level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116 cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3 cells induced the expression of RRM2. Both the cell proliferation under serum-depleted conditions and the anchorage-independent growth were impaired by the reduction of RRM2 protein expression.
  
  
  CONCLUSIONS
  RRM2 represents a novel therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in colorectal cancer with oncogenic KRAS.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Keiko
authors.initials: K
authors.lastname: Doi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Machida
authors.forename: Takeharu
authors.initials: T
authors.lastname: Ota
authors.forename: Midori
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takashima
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002455:Cell Division; D045744:Cell Line, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016895:Culture Media, Serum-Free; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras); D034741:RNA, Small Interfering / Q000494:pharmacology; D012262:Ribonucleoside Diphosphate Reductase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016895:Culture Media, Serum-Free; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins