title: Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor 1 alpha and its significance.
abstract: OBJECTIVE
  We analyzed the expressions of hexokinase II (HK II), a key enzyme in glycolysis, and VEGF in hepatocellular carcinoma (HCC) and metastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1 (HIF-1) was studied.
  
  
  METHODS
  A real-time quantitative reverse transcription-polymerase chain reaction was performed to examine the HK II and VEGF mRNA expression. Expression of HIF-1 alpha and HK II protein, and microvessel density (MVD) were examined immunohistochemically.
  
  
  RESULTS
  MVD was significantly higher in HCCs than in metastatic liver cancers, and VEGF mRNA expression was positively correlated only with MVD of HCCs. HK II mRNA expression was significantly higher in metastatic liver cancers, however, some cases of HCC pretreated with transcatheter arterial embolization (TAE) showed marked HK II mRNA expression. Both HIF-1 alpha and HK II protein expressions were co-localized in the cancer cells near necrosis, and the intensity of HIF-1 alpha protein expression was significantly correlated with HK II mRNA expression in both tumors.
  
  
  CONCLUSIONS
  These results suggest that, in metastatic liver cancers, glycolysis induced by HIF-1 is the predominant energy source under the hypoxic environment and, at least in some TAE-pretreated HCC cases, cancer cells obtain energy for growth by switching the metabolic profile to glycolysis through HIF-1.
authors.affiliation: Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, 54-Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. yasu-j@fg7.so-net.ne.jp
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
authors.forename: Akira
authors.initials: A
authors.lastname: Mori
authors.forename: Naoki
authors.initials: N
authors.lastname: Isobe
authors.forename: Weige
authors.initials: W
authors.lastname: Yang
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oe
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yonenaga
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakashita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imamura
mesh_terms: D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000473:pathology; D003199:Computer Systems; D005260:Female; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D016133:Polymerase Chain Reaction / Q000379:methods; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D006593:Hexokinase