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Updated: Apr 28, 2026
Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response
N Domanitskaya1, J Wangari-Talbot1, J Jacobs1
1Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
Background:
Resistance to chemotherapeutic agents is a major obstacle to cancer treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a source of resistance. Herein, we investigated the role of ABCC10 in mammary tumours, given the important role we have defined for ABCC10 in transporting taxanes, and the recognition that some ABCC proteins have roles in tumour growth.
Methods:
ABCC10 expression was correlated to human breast cancer subtype using breast tissue microarrays. Real-time quantitative PCR and western blot analysis were used to examine ABCC10 expression in human breast cancer lines. Abcc10(-/-) mice were crossed to MMTV-PyVmT mice to produce Abcc10(-/-) vs Abcc10(+/+) mammary tumours and derivative cell lines. We used allograft and cellular assays to perform baseline and drug sensitization analysis of tumours and cell lines.
Results:
Clinical sample analyses indicated that ABCC10 was more highly expressed in Her2+ and ER+ than in Her2-, ER-, and triple-negative breast cancer. Unexpectedly, PyVmT; Abcc10(-/-) tumours grew more rapidly than PyVmT; Abcc10(+/+) tumours and were associated with significantly reduced apoptosis and metastasis. PyVmT; Abcc10(-/-) lines were less migratory than PyVmT; Abcc10(+/+) lines. Finally, we showed increased survival of docetaxel-treated MMTV-PyVmT; Abcc10(-/-) mice compared with wild-type mice.
Conclusions:
These data identify roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.
Insights
The study reveals that ABCC10 protein is not only involved in taxane transport but also influences breast cancer growth and docetaxel resistance. Its absence unexpectedly accelerated tumor growth but sensitized tumors to docetaxel treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chemotherapeutic resistance is a significant challenge in cancer treatment.
- Multidrug Resistance Proteins (a class of ABC efflux pumps) contribute to this resistance.
- ABCC10's role in taxane transport and potential involvement in tumor growth necessitates further investigation.
Purpose of the Study:
- To investigate the role of ABCC10 in mammary tumors.
- To understand ABCC10's contribution to tumor growth and chemoresistance.
Main Methods:
- Correlation of ABCC10 expression with human breast cancer subtypes using tissue microarrays.
- Quantitative PCR and Western blot analysis of ABCC10 in breast cancer cell lines.
- Utilizing Abcc10 knockout mice crossed with MMTV-PyVmT mice to study tumor development and drug sensitivity.
Main Results:
- ABCC10 expression is higher in Her2+ and ER+ breast cancers.
- Abcc10-deficient tumors exhibited accelerated growth, reduced apoptosis, and decreased metastasis.
- Abcc10-deficient cell lines showed reduced migration.
- Abcc10-deficient mice demonstrated increased survival following docetaxel treatment.
Conclusions:
- ABCC10 plays a role in breast cancer pathogenesis.
- ABCC10 is implicated in in vivo docetaxel resistance.
