APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines
Onder Onguru1, Serap Yalcin2, Cinthia Rosemblit3
1Department of Pathology, GATA, Ankara, Turkey; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, United States.
Abstract:
APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compared expression levels with drug sensitive MCF-7 cell line. After RNAscope staining, slides were scanned and saved as digital images using Aperio scanner and software. Quantitative scoring utilizing the number of punctate dots present within each cell boundary was performed for the parameters including positive cell percentage and signal intensity per positive cell. In Doxorubicin and Etoposide resistant MCF-7 cell lines, APOBEC3B expression was approximately five-fold increased (23% and 24% respectively) with higher signal intensity (1.92 and 1.44 signal/cell, respectively) compared to drug sensitive MCF-7 cell line (5%, 1.00 signal/cell) with statistical significance. The increase of APOBEC3B expression in Docataxel resitant and Paclitaxel resistant MCF-7 cell lines was not very high. In conclusion, APOBEC3B expression was increased in some population of tumor cells of drug resistant cell lines. At least for some drugs, APOBEC3B expression may be related to drug resistance, subjecting to some tumor cells to frequent mutation.
Insights
APOBEC3B expression, a DNA-mutating enzyme, significantly increased in drug-resistant breast cancer cells. This suggests APOBEC3B may contribute to drug resistance and tumor mutation.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- APOBEC3B is a cytidine deaminase involved in DNA and RNA mutation.
- APOBEC3B-induced deamination is a known source of DNA damage in breast cancers.
- Understanding APOBEC3B's role in drug resistance is crucial for cancer treatment.
Purpose of the Study:
- To investigate APOBEC3B expression levels in drug-resistant breast cancer cell lines.
- To compare APOBEC3B expression between drug-sensitive and drug-resistant MCF-7 cell lines.
- To explore the potential link between APOBEC3B expression and drug resistance.
Main Methods:
- Utilized RNA in situ hybridization (RNAscope) for APOBEC3B detection.
- Employed digital imaging and quantitative scoring of RNAscope slides.
- Assessed parameters like positive cell percentage and signal intensity.
Main Results:
- APOBEC3B expression was significantly elevated (approx. five-fold) in Doxorubicin and Etoposide-resistant MCF-7 cells compared to sensitive cells.
- Increased signal intensity was observed in resistant cell lines.
- Modest increases in APOBEC3B expression were noted in Docetaxel and Paclitaxel-resistant cells.
Conclusions:
- APOBEC3B expression is upregulated in a subset of drug-resistant breast cancer cells.
- Elevated APOBEC3B may correlate with drug resistance in certain breast cancer contexts.
- APOBEC3B could contribute to increased tumor mutation rates in resistant cells.
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