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Updated: Jun 23, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Transcriptome changes induced by docetaxel in human mammary cell lines expressing different levels of ERBB2
M L Dos Santos1, K P Gimenes, W A Silva
1Departamento de Radiologia, Universidade de São Paulo, 01246-903, São Paulo, Brazil.
Abstract:
The taxane docetaxel is currently the most effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. Overexpression of ERBB2 occurs in 15-30% of breast tumors and is associated with chemoresistance to a variety of anticancer drugs. In the present study, we sought to identify genes involved in ERBB2-mediated chemoresistance to docetaxel. We generated SAGE libraries from two human mammary cell lines expressing basal (HB4a) and high (C5.2) levels of ERBB2 before and after intensive exposure to docetaxel and identified potential ERBB2 target genes implicated in a variety of cellular processes including cell proliferation, cell adhesion, apoptosis and cytoskeleton organization. Comparison of the transcriptome of the cell lines before and after docetaxel exposure revealed substantially different expression patterns. Twenty-one differentially expressed genes between HB4a and C5.2 cell lines, before and after docetaxel treatment, were further analyzed by qPCR. The alterations in the expression patterns in HB4a and C5.2 cell lines in response to docetaxel treatment observed by SAGE analysis were confirmed by qPCR for the majority of the genes analyzed. Our study provides a comprehensive view of the expression changes induced in two human mammary cells expressing different levels of ERBB2 in response to docetaxel that could contribute to the elucidation of the mechanisms involved in ERBB2-mediated chemoresistance in breast cancer.
Insights
This study identifies genes contributing to docetaxel resistance in breast cancer, particularly in ERBB2-overexpressing tumors. Understanding these genes may improve chemotherapy effectiveness for non-responsive patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Docetaxel is a key chemotherapy for advanced breast cancer, but resistance limits its efficacy.
- ERBB2 overexpression (15-30% of tumors) is linked to resistance against various anticancer drugs.
- Mechanisms underlying docetaxel resistance, especially ERBB2-mediated, are not fully understood.
Purpose of the Study:
- To identify genes involved in ERBB2-mediated chemoresistance to docetaxel in breast cancer.
- To compare gene expression patterns in response to docetaxel in cells with differing ERBB2 levels.
Main Methods:
- Utilized Serial Analysis of Gene Expression (SAGE) on human mammary cell lines (HB4a, C5.2) with basal and high ERBB2 levels, before and after docetaxel treatment.
- Identified differentially expressed genes related to cell proliferation, adhesion, apoptosis, and cytoskeleton organization.
- Validated gene expression changes using quantitative Polymerase Chain Reaction (qPCR).
Main Results:
- Significant differences in gene expression patterns were observed between cell lines and after docetaxel exposure.
- Twenty-one differentially expressed genes were identified and analyzed.
- qPCR confirmed SAGE findings for most analyzed genes, validating observed expression alterations.
Conclusions:
- The study provides a comprehensive analysis of gene expression changes in response to docetaxel in ERBB2-expressing breast cancer cells.
- Identified genes offer insights into ERBB2-mediated chemoresistance mechanisms.
- Findings may contribute to developing strategies to overcome docetaxel resistance in breast cancer patients.
