title: Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma.
abstract: OBJECTIVE
  Metabolic dysregulation is one of the risk factors for the development of hepatocellular carcinoma (HCC). We investigated the activated metabolic pathway in HCC to identify its role in HCC growth and mortality.
  
  
  METHODS
  Gene expression profiles of HCC tissues and non-cancerous liver tissues were obtained by serial analysis of gene expression. Pathway analysis was performed to characterize the metabolic pathway activated in HCC. Suppression of the activated pathway by RNA interference was used to evaluate its role in HCC in vitro. Relation of the pathway activation and prognosis was statistically examined.
  
  
  RESULTS
  A total of 289 transcripts were up- or down-regulated in HCC compared with non-cancerous liver (P<0.005). Pathway analysis revealed that the lipogenic pathway regulated by sterol regulatory element binding factor 1 (SREBF1) was activated in HCC, which was validated by real-time RT-PCR. Suppression of SREBF1 induced growth arrest and apoptosis whereas overexpression of SREBF1 enhanced cell proliferation in human HCC cell lines. SREBF1 protein expression was evaluated in 54 HCC samples by immunohistochemistry, and Kaplan-Meier survival analysis indicated that SREBF1-high HCC correlated with high mortality.
  
  
  CONCLUSIONS
  The lipogenic pathway is activated in a subset of HCC and contributes to cell proliferation and prognosis.
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa 920-8641, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.forename: Hajime
authors.initials: H
authors.lastname: Takatori
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Nishino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Minato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism / Q000502:physiology; D050155:Lipogenesis / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1