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Updated: Aug 18, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines
Sarah L McDonald1, David A J Stevenson, Susan E Moir
1School of Medicine, College of Life Sciences and Medicine, University of Aberdeen, Medical School, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
Abstract:
Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. In this study high-level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) were created, and comparative genomic hybridisation was used to identify genomic regions associated with resistance to docetaxel. MCF-7 resistant cells showed an amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of chromosomes 6p, 10q11.2-qter and 12p. MDA-MB-231 resistant cells showed a gain of chromosomes 5p, 7q11.1-q35, 9, and loss of chromosomes 4, 8q24.1-qter, 10, 11q23.1-qter, 12q15-q24.31, 14q and 18. Whole chromosome paints confirmed these findings. Amplification of 7q21 and loss of 10q may represent a common mechanism of acquired docetaxel resistance in breast cancer cells. This study is the first description of a genomic approach specifically to identify genomic regions involved in resistance to docetaxel.
Insights
This study identified specific genomic alterations in breast cancer cells that lead to docetaxel resistance. Understanding these genetic changes, such as amplification of 7q21 and loss of 10q, can help overcome treatment resistance.
Area of Science:
- Genomics
- Cancer Biology
- Medical Genetics
Background:
- Docetaxel is a key chemotherapy for breast cancer.
- Mechanisms of docetaxel resistance in breast cancer are not fully understood.
- Identifying genetic factors contributing to resistance is crucial for improving treatment efficacy.
Purpose of the Study:
- To identify genomic regions associated with docetaxel resistance in human breast cancer cell lines.
- To investigate potential common genomic mechanisms underlying acquired docetaxel resistance.
Main Methods:
- Development of high-level docetaxel-resistant MCF-7 and MDA-MB-231 breast cancer cell lines.
- Comparative genomic hybridization (CGH) to detect chromosomal gains and losses.
- Whole chromosome painting to confirm CGH findings.
Main Results:
- Docetaxel-resistant MCF-7 cells exhibited amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of 6p, 10q11.2-qter, 12p.
- Resistant MDA-MB-231 cells showed gain of 5p, 7q11.1-q35, 9, and loss of 4, 8q24.1-qter, 10, 11q23.1-qter, 12q15-q24.31, 14q, 18.
- Amplification of 7q21 and loss of 10q were identified as potential common mechanisms of acquired resistance.
Conclusions:
- This study provides the first genomic description of regions involved in docetaxel resistance in breast cancer.
- Amplification of 7q21 and loss of 10q may be key contributors to acquired docetaxel resistance.
- Genomic profiling offers a novel approach to understanding and potentially overcoming chemotherapy resistance.
