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Updated: Jun 2, 2026

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
Genomic profiling of decreased DNA damage response in human squamous carcinoma cells
1University of Illinois Cancer Center, Chicago, IL 60612, USA.
Abstract:
A significant problem in the use of radiation and chemotherapy drugs is the development of resistance to these agents by recurrent and metastatic tumors. A number of mechanisms have been proposed for chemotherapy and radiation resistance. Previous studies have suggested that resistant cancer cells are more tolerant of DNA damage than sensitive cells. Overexpression of the multiple drug resistance gene P-glycoprotein, which acts as a drug efflux pump, has been implicated in drug resistance. The glutathione-S-X gene has also been shown to be involved in drug resistance. The increased expression of a number of proto-oncogenes, including AP-1, c-myc and ras, has been associated with chemotherapy resistance. Given the number of reported radi-ation and chemotherapy resistance genes in cancer, we took a global gene expression approach to examine differences between sensitive and resistant cells and their response to different types of DNA damage. We demonstrated increased numbers of responsive genes in sensitive normal epidermal keratinocytes compared to resistant squamous cell carcinoma cells, regardless of the type of DNA damage. Our results also show new genes that may be responsible for chemotherapy resistance in cancer cells, and differences in how sensitive and resistant cells respond to specific types of DNA damage.
Insights
Chemotherapy and radiation resistance in cancer is a major challenge. This study identified new genes and response differences in sensitive versus resistant cancer cells, offering insights into overcoming treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Chemotherapy and radiation resistance in recurrent and metastatic tumors is a significant clinical problem.
- Mechanisms of resistance include DNA damage tolerance, P-glycoprotein efflux pumps, glutathione-S-X involvement, and proto-oncogene overexpression (AP-1, c-myc, ras).
Purpose of the Study:
- To investigate global gene expression differences between sensitive and resistant cancer cells.
- To understand how sensitive and resistant cells respond to various types of DNA damage.
Main Methods:
- Global gene expression profiling was employed to compare sensitive and resistant cell lines.
- Analysis focused on differential gene responsiveness to different DNA damaging agents.
Main Results:
- Sensitive normal epidermal keratinocytes exhibited a greater number of responsive genes compared to resistant squamous cell carcinoma cells, irrespective of DNA damage type.
- Identified novel genes potentially involved in chemotherapy resistance.
- Observed distinct response patterns to specific DNA damage types between sensitive and resistant cells.
Conclusions:
- Gene expression patterns differ significantly between sensitive and resistant cancer cells.
- Understanding these differences and cellular responses to DNA damage can reveal new therapeutic targets for overcoming resistance.
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