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Updated: Feb 19, 2026
12:02
Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
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The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1.
Miyoung Lee1, Yainyrette Rivera-Rivera2, Carlos S Moreno3
1Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Oncotarget
|November 5, 2017
Summary
E2F activators regulate cell proliferation and genomic stability. This study reveals E2F activation in breast cancer correlates with poor survival and identifies Sgo1 and BubR1 as key regulators of mitosis and chromosome integrity.
Area of Science:
- Cell Biology
- Cancer Biology
- Genetics
Background:
- E2F activators (E2F1, E2F2, E2F3a) are crucial for cell proliferation.
- Centrosome amplification (CA) and spindle assembly checkpoint (SAC) dysfunction drive aneuploidy and chromosome instability (CIN) in cancer.
- The role of E2F activators in regulating mitosis and maintaining genomic integrity remains largely unknown.
Purpose of the Study:
- To investigate how E2F activators regulate mitosis and genomic integrity.
- To explore the correlation between E2F overexpression and clinical outcomes in breast cancer.
- To elucidate the distinct mechanisms by which Sgo1 and BubR1 maintain genomic stability.
Main Methods:
- Overexpression of E2F activators in mammary epithelial cells.
- Analysis of TCGA database using cBioPortal.
- Kaplan-Meier survival analysis.
- Transient knockdown of Sgo1 and BubR1 in MCF10A cells.
Main Results:
- Combined E2F overexpression did not enhance CA but elevated mitotic regulators (Sgo1, Nek2, Hec1, BubR1, Mps1/TTK).
- E2F overexpression in breast tumors correlates with increased expression of chromosome segregation and SAC regulators.
- Overexpression of E2F1, E2F3a, Mps1/TTK, Nek2, BubR1, or Hec1 is linked to poor patient survival.
- Sgo1 knockdown induced CA and chromosome loss, while BubR1 silencing caused chromosome loss without CA.
Conclusions:
- Deregulated E2F activation in mammary cells is counteracted by a Sgo1-dependent mitotic checkpoint.
- Sgo1 and BubR1 safeguard genomic integrity through distinct pathways.
- E2F activators and associated mitotic regulators represent potential therapeutic targets in breast cancer.
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