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Updated: Jul 2, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver
10:06

Cell Type-specific Gene Expression Profiling in the Mouse Liver

Published on: September 17, 2019

Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest

Jennifer W-M Gho1, Wai-Ki Ip, Kathy Y-Y Chan

  • 1Li Ka-Shing Institute of Health Sciences, Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Cancer Research
|August 15, 2008
PubMed

Insights

Down-regulation of the transcription factor ATF5 is common in hepatocellular carcinoma (HCC), inhibiting tumor growth and causing cell cycle arrest. ID1 is identified as a downstream target, suggesting ATF5 acts as a tumor suppressor in HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Transcription factors regulate crucial cellular processes like proliferation and cell cycle.
  • Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis.
  • ATF5 (Activating Transcription Factor 5) is a transcription factor implicated in various cellular functions.

Purpose of the Study:

  • To investigate the role of ATF5 in hepatocellular carcinoma (HCC).
  • To identify downstream targets and regulatory mechanisms of ATF5 in HCC.
  • To explore ATF5 as a potential therapeutic target for HCC.

Main Methods:

  • Array-based mapping and quantitative reverse transcription-PCR to assess ATF5 expression in HCC tumors and adjacent non-tumoral liver.
  • Restoration of ATF5 expression in HCC cell lines to evaluate its effect on proliferation, apoptosis, and cell cycle.
  • Array profiling to identify differentially expressed genes and electromobility shift assays to confirm ATF5-ID1 interaction.
  • Analysis of potential mechanisms for ATF5 silencing, including copy number loss, promoter hypermethylation, histone deacetylation, and DNA mutations.

Main Results:

  • Consistent down-regulation of ATF5 was observed in 78% of HCC tumors compared to non-tumoral liver tissue.
  • Restoring ATF5 expression in HCC cell lines significantly inhibited growth and induced G2-M cell cycle arrest.
  • ID1 was identified as a downstream target of ATF5, with an inverse expression relationship and direct promoter interaction.
  • Mechanisms contributing to ATF5 silencing in HCC include copy number losses, promoter hypermethylation, histone deacetylation, and DNA mutations.

Conclusions:

  • ATF5 plays a tumor-suppressive role in hepatocellular carcinoma.
  • ID1 is a key downstream target regulated by ATF5 in HCC.
  • Understanding ATF5 regulation and function provides insights into HCC pathogenesis and potential therapeutic strategies.

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