Related Experiment Video
Updated: Jun 8, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Glycogen synthase kinase-3beta: a prognostic marker and a potential therapeutic target in human bladder cancer
Sei Naito1, Vladimir Bilim, Kaori Yuuki
1Laboratory of Molecular Oncology, Department of Urology, Yamagata University School of Medicine, Yamagata, Japan.
Purpose:
Although recent studies have shown glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase, as a positive regulator of pancreatic, colon, and kidney cancer cell survival and proliferation, the role of GSK-3 in bladder cancer remains unknown. Our objectives were to determine the subcellular localization of GSK-3β and to evaluate the effect of GSK-3 inhibition in bladder cancer.
Experimental Design:
We used immunohistochemical staining and nuclear/cytosolic fractionation to determine the expression pattern of GSK-3β in human urothelial carcinomas. To study the effect of GSK-3 inhibition on bladder cancer cell proliferation and survival, we used pharmacologic inhibitors of GSK-3, RNA interference, MTS assay, bromodeoxyuridine incorporation assay, quantitative reverse transcriptase-PCR, and Western blotting.
Results:
We found aberrant nuclear accumulation of GSK-3β in 62% (43 of 69) and 91% (21 of 23) of noninvasive and invasive human urothelial carcinomas, respectively. GSK-3β nuclear staining was significantly associated with high-grade tumors (P < 0.001), advanced stage of bladder cancer (P < 0.05), metastasis (P < 0.05), and worse cause-specific survival (P < 0.05) in bladder cancer patients. Moreover, we found that pharmacologic inhibition or genetic depletion of GSK-3β resulted in decreased viability of bladder cancer cells.
Conclusions:
Our results suggest nuclear accumulation of GSK-3β as a novel prognostic marker in bladder cancer, show that GSK-3 contributes to urothelial cancer cell proliferation and survival, and identify GSK-3 as a potential therapeutic target in human bladder cancer.
Insights
Glycogen synthase kinase-3 beta (GSK-3β) is found in the nucleus of bladder cancer cells, indicating it is a potential therapeutic target. Inhibition of GSK-3β reduces bladder cancer cell survival and proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase implicated in the survival and proliferation of various cancer cells.
- The role of GSK-3 in bladder cancer pathogenesis is currently unknown.
Purpose of the Study:
- To investigate the subcellular localization of GSK-3β in bladder cancer.
- To determine the effect of GSK-3 inhibition on bladder cancer cell proliferation and survival.
Main Methods:
- Immunohistochemical staining and nuclear/cytosolic fractionation to assess GSK-3β expression in urothelial carcinomas.
- Pharmacologic inhibition and RNA interference were used to study GSK-3 inhibition.
- Cell viability, proliferation, gene expression, and protein levels were analyzed using MTS assay, BrdU incorporation, qRT-PCR, and Western blotting.
Main Results:
- Aberrant nuclear accumulation of GSK-3β was observed in 62% of noninvasive and 91% of invasive urothelial carcinomas.
- GSK-3β nuclear staining correlated with high-grade tumors, advanced stage, metastasis, and worse survival in bladder cancer patients.
- Inhibition or genetic depletion of GSK-3β significantly decreased bladder cancer cell viability.
Conclusions:
- Nuclear GSK-3β accumulation serves as a novel prognostic marker for bladder cancer.
- GSK-3 plays a crucial role in urothelial cancer cell proliferation and survival.
- GSK-3 represents a potential therapeutic target for human bladder cancer.