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C/EBPα inhibits hepatocellular carcinoma by reducing Notch3/Hes1/p27 cascades

Yi-Chao Shi1, Hong Zhao, Chuan Yin

  • 1Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|July 3, 2013
PubMed
Abstract

Insights

CCAAT/enhancer binding protein α (C/EBPα) inhibits liver cancer growth by reducing tumor cell proliferation and re-establishing liver-specific gene expression. C/EBPα shows therapeutic potential for hepatocarcinogenesis by targeting the Notch3/Hes1/p27 pathway.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cancer Research

Background:

  • CCAAT/enhancer binding protein α (C/EBPα) is a key transcription factor in liver cell function.
  • The role of C/EBPα in hepatocarcinogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of C/EBPα in hepatocarcinogenesis.
  • To determine the therapeutic potential of C/EBPα in liver cancer.

Main Methods:

  • Constructed a recombinant adenovirus carrying the C/EBPα gene.
  • Assessed the effects of C/EBPα on hepatocarcinogenesis in vitro and in vivo models.

Main Results:

  • Overexpression of C/EBPα inhibited tumor cell growth, re-established liver-specific gene expression, and induced cell cycle arrest.
  • C/EBPα suppressed proliferation of cancer cells and fibroblasts, reduced tumor xenograft growth, and eradicated orthotopic liver tumors.
  • C/EBPα reduced Notch3 expression, suppressing Hes1 activity and decreasing p27 levels, partially reversing the anti-proliferation effects.

Conclusions:

  • C/EBPα exerts its anti-hepatocarcinogenesis effects partly via the Notch3/Hes1/p27 pathway.
  • C/EBPα demonstrates significant therapeutic potential for human hepatocarcinogenesis.
Keywords:
C/EBPαHepatocellular carcinomaHes1Notch3

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