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Updated: Mar 14, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis
Qiu-Lin Ge1, San-Hong Liu2, Zhi-Hong Ai1
1Department of Obstetrics and Gynecology, The Sixth People's Hospital affiliated with Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.
Insights
Nuclear factor-kappa B (NF-κB) RelB protein is highly expressed in endometrial cancer (EC), particularly endometrioid adenocarcinoma. Increased RelB promotes EC cell growth and tumorigenicity, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Nuclear factor-kappa B (NF-κB) signaling pathway is crucial in various human cancers.
- While NF-κB gene family involvement in endometrial carcinogenesis is known, central regulator roles remain unclear.
Purpose of the Study:
- Investigate the specific roles of canonical and noncanonical NF-κB signaling in endometrial cancer (EC) development.
- Determine the expression levels and functional significance of NF-κB regulators in EC.
Main Methods:
- Analyzed NF-κB RelB and RelA protein expression in EC tissues and cell lines.
- Assessed the impact of RelB modulation on key cell cycle, apoptosis, and proliferation regulators (c-Myc, cyclin D1, Bcl-2, Bcl-xL, p27) in EC cells.
Main Results:
- NF-κB RelB protein, not RelA, showed significantly high expression in EC, especially endometrioid adenocarcinoma (EEC).
- Tumor cell-intrinsic RelB drives elevated c-Myc, cyclin D1, Bcl-2, and Bcl-xL, promoting cell growth and inhibiting apoptosis in EEC.
- RelB depletion led to increased p27 expression, a cell cycle inhibitor.
Conclusions:
- Elevated RelB in human EC correlates with enhanced EEC cell proliferation and tumorigenicity.
- RelB within the noncanonical NF-κB pathway represents a potential therapeutic target for blocking EC initiation.
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