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Updated: Aug 15, 2026

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
The expression of the ubiquitin ligase subunit Cks1 in human breast cancer
Merav Slotky1, Ma'anit Shapira, Ofer Ben-Izhak
1Department of Surgery A, Rambam Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel. m_slotky@rambam.health.gov.il
Introduction:
Loss of the cell-cycle inhibitory protein p27Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27Kip1 and Skp2 expression and to tumor aggressiveness.
Methods:
The expressions of Cks1, Skp2, and p27Kip1 were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan-Meier method.
Results:
The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27Kip1 (r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen.
Conclusion:
These results suggest that Cks1 is involved in p27Kip1 down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer.
Insights
Cyclin-dependent kinase subunit 1 (Cks1) overexpression in breast cancer correlates with poor prognosis by decreasing the cell-cycle inhibitor p27Kip1. Cks1 may drive aggressive tumor behavior and warrants further investigation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Loss of p27Kip1, a cell-cycle inhibitor, is linked to poor breast cancer prognosis.
- p27Kip1 degradation is regulated by Skp2 and Cks1, its ubiquitin ligase subunits.
- Skp2 is overexpressed in breast cancer, but Cks1's role remains unclear.
Purpose of the Study:
- To investigate the role of Cks1 expression in breast cancer.
- To examine the relationship between Cks1, p27Kip1, and Skp2 expression.
- To determine Cks1's association with tumor aggressiveness.
Main Methods:
- Immunohistochemistry and immunoblot analysis of Cks1, Skp2, and p27Kip1 expression in patient tissues and cell lines.
- Statistical analysis using Cox regression and Kaplan-Meier methods to correlate Cks1 levels with clinical parameters.
Main Results:
- Cks1 expression strongly correlated with Skp2 and inversely with p27Kip1.
- Cks1 overexpression was linked to poor tumor differentiation, younger age, loss of hormone receptors, and reduced survival.
- Estradiol increased Cks1/Skp2, while tamoxifen decreased them in cell lines.
Conclusions:
- Cks1 contributes to p27Kip1 downregulation in breast cancer.
- Cks1 plays a significant role in the development of aggressive breast cancer phenotypes.
- Targeting Cks1 may offer a therapeutic strategy for aggressive breast cancer.
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