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Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines

Mizuho Tanabe1, Hiroto Izumi, Tomoko Ise

  • 1Departments of Molecular Biology and. Surgery II, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Fukuoka, Japan.

Cancer Research
|December 26, 2003
PubMed

Insights

Activating transcription factor 4 (ATF4) expression correlates with cisplatin sensitivity in lung cancer. Higher ATF4 levels may predict reduced sensitivity to cisplatin chemotherapy, aiding treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Cisplatin resistance is a significant challenge in solid tumor treatment.
  • Identifying molecular determinants of cisplatin resistance is crucial for improving therapeutic outcomes.

Purpose of the Study:

  • To identify genes involved in cisplatin resistance.
  • To investigate the role of activating transcription factor 4 (ATF4) in cisplatin sensitivity.

Main Methods:

  • Differential display of mRNA to identify cisplatin-inducible genes.
  • Northern blot analysis to assess ATF4 expression.
  • Correlation analysis of ATF4 levels with cisplatin sensitivity in 11 human lung cancer cell lines.
  • Overexpression studies in stable transfectants.

Main Results:

  • Activating transcription factor 4 (ATF4) was identified as a cisplatin-inducible gene.
  • ATF4 expression is transcriptionally regulated and upregulated in cisplatin-resistant cell lines.
  • ATF4 expression levels significantly correlated with cisplatin sensitivity (P = 0.01).
  • Overexpression of ATF4 reduced sensitivity to cisplatin but not vincristine.

Conclusions:

  • Cellular levels of ATF4 are linked to cisplatin sensitivity.
  • ATF4 expression may serve as a predictive biomarker for cisplatin response in lung cancer.

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