Egr-1 suppresses breast cancer cells proliferation by arresting cell cycle progression via down-regulating CyclinDs
Lu-Lu Wei1, Xiao-Jin Wu2, Chan-Chan Gong1
1Department of Pathology, Xuzhou Medical University Xuzhou 221004, China.
Abstract:
Egr-1 is an important nuclear transcription factor in the early growth response gene family (Egr family). Egr-1 was reportedly involved in the tumorigenesis of diverse tumors. However, there was a paucity of data regarding the role of Egr-1 in the breast cancer. Herein, we investigated the expression of Egr-1 in breast tissues and breast cancer cell lines BT549 and Bcap37. Immunohistochemistry showed that Egr-1 was down-regulated in breast cancer tissues versus the normal paracancerous tissues. Overexpression of Egr-1 could arrest the progression of cell cycle in breast cancer cells. Luciferase reporter assay revealed Egr-1 could bind to the promoters of CyclinD1, CyclinD2 and CyclinD3. Together, these results suggested that Egr-1 could affect the cell cycle of breast cancer cells and defined the mechanism for the cells by inhibiting the process of G0/G1 phase. Our findings provide new insight into Egr-1 in breast cancer.
Insights
Early growth response protein 1 (Egr-1) is downregulated in breast cancer, inhibiting cell cycle progression. Egr-1 overexpression arrests breast cancer cells at the G0/G1 phase by targeting cell cycle genes.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Early growth response protein 1 (Egr-1) is a nuclear transcription factor implicated in tumorigenesis across various cancers.
- Limited data exists on the specific role of Egr-1 in breast cancer development and progression.
Purpose of the Study:
- To investigate the expression levels of Egr-1 in breast cancer tissues and cell lines.
- To elucidate the functional role of Egr-1 in regulating breast cancer cell cycle progression.
Main Methods:
- Immunohistochemistry was employed to assess Egr-1 expression in breast tissues.
- Breast cancer cell lines (BT549 and Bcap37) were utilized for functional studies.
- Luciferase reporter assays were performed to determine Egr-1's interaction with target gene promoters.
Main Results:
- Egr-1 expression was found to be significantly downregulated in breast cancer tissues compared to adjacent normal tissues.
- Overexpression of Egr-1 led to the arrest of cell cycle progression in breast cancer cells.
- Egr-1 was identified to bind to the promoter regions of CyclinD1, CyclinD2, and CyclinD3, inhibiting the G0/G1 phase.
Conclusions:
- Egr-1 plays a critical role in regulating the cell cycle of breast cancer cells.
- The mechanism involves the inhibition of the G0/G1 phase, potentially through the regulation of Cyclin D genes.
- These findings offer novel insights into the function of Egr-1 in breast cancer, suggesting its potential as a therapeutic target.
Related Concept Videos
Inhibition of Cdk Activity
Negative Regulator Molecules
Mitogens and the Cell Cycle
Abnormal Proliferation
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...


