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Updated: Jul 5, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
Damaged DNA binding protein 2 plays a role in breast cancer cell growth
Zilal Kattan1, Sophie Marchal, Emilie Brunner
1Laboratoire de Biologie Cellulaire du Développement, EA 3446 Université Henri Poincaré-Nancy Université, Vandoeuvre-lès-Nancy, France.
Abstract:
The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer.
Insights
Damaged DNA binding protein 2 (DDB2) acts as an oncogene in breast cancer, promoting cell growth and colony formation, particularly in estrogen receptor-positive tumors. DDB2 may serve as a predictive marker for breast cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Damaged DNA binding protein 2 (DDB2) is involved in DNA repair, transcription, and cell cycle regulation.
- Loss of DDB2 function is potentially linked to tumor susceptibility.
- This study investigated the role of DDB2 in breast cancer cell growth, focusing on its interaction with the E2F1 marker.
Purpose of the Study:
- To determine if DDB2 plays a role in breast cancer cell proliferation.
- To explore DDB2's potential as a predictive marker in breast cancer.
Main Methods:
- Gene expression analysis in breast cancer cell lines and patient tumor samples.
- DDB2 knockdown using small interfering RNA (siRNA) in MCF-7 cells.
- DDB2 gene introduction into MDA-MB231 cells.
- Flow cytometry for cell cycle analysis and proliferation assessment (5-Bromodeoxyuridine incorporation).
- Analysis of S phase marker expression (PCNA, cyclin E, DHFR).
Main Results:
- DDB2 was overexpressed in estrogen receptor (ER)-positive breast cancer cells and tumor samples compared to ER-negative counterparts.
- DDB2 knockdown inhibited growth and colony formation in MCF-7 cells.
- DDB2 introduction stimulated growth and colony formation in MDA-MB231 cells.
- DDB2 knockdown led to delayed G1/S transition and slowed S phase progression, with decreased expression of S phase markers.
Conclusions:
- DDB2 functions as an oncogene in breast cancer, promoting cell growth.
- DDB2 expression is associated with ER-positive breast cancer.
- DDB2 is a potential predictive marker for breast cancer.
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