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Oncogenic H-Ras up-regulates expression of ERCC1 to protect cells from platinum-based anticancer agents

Cha-Kyung Youn1, Mi-Hwa Kim, Hyun-Ju Cho

  • 1Research Center for Proteineous Materials, School of Medicine, Chosun University, Gwangju, Korea.

Cancer Research
|July 17, 2004
PubMed

Insights

Oncogenic Ras mutations activate DNA repair by up-regulating ERCC1, enhancing cancer cell resistance to platinum chemotherapy. Targeting ERCC1 may overcome this resistance, improving treatment efficacy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Ras gene mutations are common in tumors, leading to constitutive activation of the Ras signaling pathway.
  • Ras pathway activation contributes to tumor progression and resistance to platinum-based chemotherapy.

Purpose of the Study:

  • To investigate the mechanisms by which activated H-Ras influences the expression of nucleotide excision repair genes.
  • To determine the role of ERCC1 in H-Ras-mediated chemoresistance.

Main Methods:

  • Analysis of activated H-Ras effects on nucleotide excision repair gene expression.
  • Promoter analysis of the ERCC1 gene.
  • Use of ERCC1 small interfering RNA (siRNA) to assess its role in DNA repair and chemoresistance.

Main Results:

  • Activated H-Ras markedly up-regulates ERCC1, a key enzyme in nucleotide excision repair.
  • Increased AP1 transcriptional activity, driven by oncogenic H-Ras, is crucial for ERCC1 induction.
  • ERCC1 siRNA reduced H-Ras-mediated DNA repair activity and platinum-based chemoresistance.

Conclusions:

  • Oncogenic H-Ras induces ERCC1, enhancing DNA repair capacity.
  • This H-Ras-induced ERCC1 may protect cancer cells from platinum-based anticancer agents.
  • Targeting ERCC1 could be a strategy to overcome Ras-mediated chemoresistance.

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