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Updated: Aug 10, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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Gene expression and amplification in breast carcinoma cells with intrinsic and acquired doxorubicin resistance

N J Turton1, D J Judah, J Riley

  • 1MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester, LE1 9HN UK.

Oncogene
|April 21, 2001
PubMed

Insights

Multidrug resistance (MDR) in cancer is linked to specific gene expression patterns. Identifying these genes offers new diagnostic tools and potential therapeutic targets for doxorubicin resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Multidrug resistance (MDR) is a significant obstacle in successful cancer chemotherapy.
  • Doxorubicin (DOX) resistance, both intrinsic and acquired, necessitates a deeper understanding of underlying molecular mechanisms.

Purpose of the Study:

  • To analyze gene expression profiles associated with doxorubicin resistance.
  • To identify novel diagnostic markers and therapeutic targets for overcoming MDR.

Main Methods:

  • Gene expression analysis of 4224 genes in relation to doxorubicin resistance.
  • Comparative analysis between carcinoma cells and a normal breast epithelial cell line (HBL100).
  • Genomic amplification and deletion analysis.

Main Results:

  • A distinct cluster of overexpressed genes associated with DOX resistance was identified, including ABCB1, MMP1, and OXTR.
  • Overexpression of genes involved in xenobiotic metabolism, cell signaling, and lymphocyte activation correlated with DOX resistance.
  • Specific genetic alterations, such as ABCB1, PGY3 (ABCB4), and BAK, were common in both intrinsic and acquired DOX resistance.
  • Keratins 8 and 18, regulated by the ras signaling pathway, were overexpressed in carcinoma cells.

Conclusions:

  • Gene expression profiling provides new avenues for diagnosing doxorubicin resistance.
  • The oxytocin receptor (OXTR) and other identified genes represent potential novel therapeutic targets for MDR cancers.

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