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Updated: Feb 2, 2026

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System
Published on: April 23, 2021
Aberrant expression of glycogen synthase kinase-3β in human breast and head and neck cancer
Andrey V Ugolkov1,2, Maria Matsangou1, Timothy J Taxter3
1Department of Medicine, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Abstract:
Glycogen Synthase Kinase-3β (GSK-3β), a serine/threonine protein kinase, has been implicated as a potential therapeutic target in human cancer. The objective of the present study was to evaluate aberrant expression of GSK-3β as a potential biomarker in human breast and head and neck cancers. Nuclear/cytosolic fractionation, immunoblotting and immunohistochemical staining was used to study the expression of GSK-3β in human breast and head and neck cancer. Aberrant nuclear accumulation of GSK-3β in five human breast cancer cell lines was demonstrated and in 89/128 (70%) human breast carcinomas, whereas no detectable expression of GSK-3β was found in benign breast tissue. Nuclear GSK-3β expression was associated with HER-2 positive tumors (P=0.02) and non-triple negative breast carcinomas (P=0.0001), although nuclear GSK-3β was observed in some samples across all breast cancer subtypes. Aberrant nuclear expression of GSK-3β was found in 11/15 (73%) squamous cell head and neck carcinomas, whereas weak or no detectable expression of GSK-3β was found in benign salivary gland and other benign head and neck tissues. These results support the hypothesis that aberrant nuclear GSK-3β may represent a potential target for the clinical treatment of human breast and squamous cell carcinoma.
Insights
Aberrant nuclear accumulation of Glycogen Synthase Kinase-3β (GSK-3β) was observed in most breast and head and neck cancers. This finding suggests GSK-3β may be a potential therapeutic target for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glycogen Synthase Kinase-3β (GSK-3β) is a serine/threonine protein kinase implicated in human cancer.
- Aberrant GSK-3β expression is a potential biomarker for cancer diagnosis and treatment.
Purpose of the Study:
- To evaluate the aberrant expression of GSK-3β as a potential biomarker in human breast and head and neck cancers.
- To investigate the clinical significance of GSK-3β expression in different cancer subtypes.
Main Methods:
- Utilized nuclear/cytosolic fractionation, immunoblotting, and immunohistochemical staining.
- Analyzed GSK-3β expression in human breast cancer cell lines, breast carcinomas, and benign breast tissue.
- Examined GSK-3β expression in squamous cell head and neck carcinomas and benign head and neck tissues.
Main Results:
- Demonstrated aberrant nuclear GSK-3β accumulation in five human breast cancer cell lines and 70% of human breast carcinomas.
- Found no detectable GSK-3β expression in benign breast tissue.
- Observed aberrant nuclear GSK-3β expression in 73% of squamous cell head and neck carcinomas, with minimal expression in benign tissues.
- Associated nuclear GSK-3β expression with HER-2 positive and non-triple negative breast carcinomas.
Conclusions:
- Aberrant nuclear GSK-3β expression is a prevalent finding in breast and head and neck squamous cell carcinomas.
- GSK-3β may serve as a potential therapeutic target for clinical treatment of these cancers.
- Further research into GSK-3β targeted therapies is warranted.
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