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.