title: Late SV40 factor: a key mediator of Notch signaling in human hepatocarcinogenesis.
abstract: OBJECTIVE
  To investigate the relationship between late SV40 factor (LSF) and Notch signaling in the development and progress of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry. The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines, including hepatic stellate cells (HSC) and human embryonic kidney epithelial cells (HEK).
  
  
  RESULTS
  Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples (76%, 19/25, P < 0.0001 and 84%, 21/25, P < 0.0001, respectively) compared with non-cancer samples. Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells. Furthermore, blocking Notch-1 activation with a γ-secretase inhibitor, DAPT, downregulated LSF expression in HepG2 cells. Additionally, a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.
  
  
  CONCLUSIONS
  LSF is a key mediator of the Notch signaling pathway, suggesting that it might be a novel therapeutic target for the treatment of HCC.
authors.affiliation: Department of Pathology, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China.
authors.forename: Ren-Hua
authors.initials: RH
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Ping-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C501906:TFCP2 protein, human; D014157:Transcription Factors