Aberrant expression of glycogen synthase kinase-3β in human breast and head and neck cancer

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.

Keywords: GSK-3; breast cancer; expression; head and neck cancer; nuclear.

Figure 1.

GSK-3β is aberrantly accumulated in the nucleus of breast cancer cells. (A) Representative image of GSK-3β expression and localization in primary breast carcinoma and adjacent benign breast tissue. Nuclear GSK-3β is expressed selectively in breast cancer cells. Scale bar, 50 µm. (B) Nuclear and cytosolic protein extracts were prepared from breast cancer cell lines, 50 µg of nuclear and cytosolic proteins were separated by SDS-PAGE, transferred to PVDF membrane, and immunoblotted as indicated. GSK-3, Glycogen Synthase Kinase-3.

Figure 2.

Nuclear expression of GSK-3β in human breast carcinoma. Representative pictures of nuclear GSK-3β expression in primary breast carcinoma, case 1 (A), and primary breast carcinoma, case 2 (B) with corresponding lymph node metastasis, case 2 (C). Scale bar, 50 µm. GSK-3, Glycogen Synthase Kinase-3.

Figure 3.

GSK-3β expression in head and neck malignant and benign tissues. Representative images of GSK-3β expression and localization in benign salivary gland (A) and squamous cell carcinoma (B). Scale bar, 50 µm. GSK-3, Glycogen Synthase Kinase-3.