title: Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis.
abstract: BACKGROUND
  Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).
  
  
  METHODS
  RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.
  
  
  RESULTS
  RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90±8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31±4% and 4±1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.
  
  
  CONCLUSIONS
  RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishina
authors.forename: Shigetomi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsubara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Masaya
authors.initials: M
authors.lastname: Iwamuro
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takaoka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Uemura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hagihara
authors.forename: Junichi
authors.initials: J
authors.lastname: Toshimori
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D050677:Core Binding Factor Alpha 3 Subunit; D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C493729:Runx3 protein, human; D020169:Caspases