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Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Different morphological structures of breast tumors demonstrate individual drug resistance gene expression profiles
T S Gerashchenko1, E V Denisov2, N M Novikov3
1Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk 634050, Russia.
Aim:
To identify gene expression profiles involved in drug resistance of different morphological structures (tubular, alveolar, solid, trabecular, and discrete) presented in breast cancer.
Material And Methods:
Ten patients with luminal breast cancer have been included. A laser microdissection-assisted microarrays and qRT-PCR were used to perform whole-transcriptome profiling of different morphological structures, to select differentially expressed drug response genes, and to validate their expression.
Results:
We found 27 differentially expressed genes (p < 0.05) encoding drug uptake (SLC1A3, SLC23A2, etc.) and efflux (ABCC1, ABCG1, etc.) transporters, drug targets (TOP2A, TYMS, and Tubb3), and proteins that are involved in drug detoxification (NAT1 and ALDH1B1), cell cycle progression (CCND1, AKT1, etc.), apoptosis (CASP3, TXN2, etc.), and DNA repair (BRCA1 and USP11). Each type of structures showed an individual gene expression profile related to resistance and sensitivity to anticancer drugs. However, most of the genes (19/27; p < 0.05) were expressed in alveolar structures. Functional enrichment analysis showed that drug resistance is significantly associated with alveolar structures. Other structures demonstrated the similar number (10-13 out of 27) of expressed genes; however, the spectrum of resistance and sensitivity to different anticancer drugs varied.
Conclusion:
Different morphological structures of breast cancer show individual expression of drug resistance genes.
Insights
Breast cancer
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Breast cancer exhibits diverse morphological structures, including tubular, alveolar, solid, trabecular, and discrete forms.
- Understanding the molecular basis of drug resistance in these distinct structures is crucial for effective cancer treatment.
Purpose of the Study:
- To identify gene expression profiles associated with drug resistance in different breast cancer morphological structures.
- To elucidate how specific gene expression patterns in these structures influence sensitivity or resistance to anticancer drugs.
Main Methods:
- Whole-transcriptome profiling using laser microdissection-assisted microarrays and quantitative real-time PCR (qRT-PCR).
- Analysis of gene expression in ten patients with luminal breast cancer across various morphological subtypes.
- Identification and validation of differentially expressed genes related to drug response.
Main Results:
- Identified 27 differentially expressed genes (p < 0.05) involved in drug uptake, efflux, targeting, detoxification, cell cycle, apoptosis, and DNA repair.
- Each morphological structure displayed a unique gene expression profile linked to drug resistance and sensitivity.
- Alveolar structures showed the highest expression of these genes (19/27), significantly associated with drug resistance.
Conclusions:
- Distinct morphological structures within breast cancer possess individual gene expression profiles that dictate drug resistance.
- Targeting specific gene expression patterns in different structures may offer novel therapeutic strategies for breast cancer.
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