Abstract
BackgroundThe study aims to evaluate the expression and activity of glycogen synthase kinase 3 isoforms α/β (GSK3α/β) and to assess their oncogenic potential through a correlation with the expression of cyclin D1 and p53 in oral cancer.MethodsThe expression of total and phosphorylated GSK3α/β as well as cyclin D1 and p53 together with their interaction were assessed in human oral cancer tissue samples, apparently normal adjacent tissues, benign tumor samples, premalignant lesions and healthy normal tissues (total 179) using various methods, such as immunohistochemistry, Western blot assays, immunoprecipitation and RT-PCR analysis.ResultsThe expression of GSK3β was significantly higher relative to GSK3α indicating the greater role of the β isoform in oral cancer. Among various types of oral cancers, OSCC (of the lip and tongue) showed elevated expression of GSK3α/β, and the expression was correlated with disease progression. The increased expression of pS21GSK3α and pS9GSK3β not only correlated positively with cyclin D1 and p53 expression in tongue cancer progression but a gradual shift of their expression from the cytoplasmic to the nuclear compartment and overall disease severity was also observed. The interaction of GSK3β-cyclin D1 and the positive correlation of pS9GSK3β and the transcription of cyclin D1 were observed.ConclusionsThese results demonstrate that the inactivation of GSK3β is an important event in OSCC and can be used as a marker for assessing disease severity and may be exploited for therapeutic intervention.
Highlights
Oral cancer is the sixth most common cancer in the world, and its incidence varies in different ecogeographic regions [1,2]
Protein expression of GSK3β is higher than GSK3α in different types of oral tumors GSK3 immunoreactivity was observed, and different tumors showed the expression of both of the proteins (GSK3α/β) to different extents
The age group >40 ≤ 70 showed expression and overexpression of GSK3β compared to GSK3α, and this observation was statistically significant
Summary
Oral cancer is the sixth most common cancer in the world, and its incidence varies in different ecogeographic regions [1,2]. The high incidence of oral cancer in the Jharkhand state in the eastern part of India may be attributed to use of locally made alcoholic beverages, such as Mohua prepared from. GSK3 proteins usually have three domains, a small N-terminal domain, a slightly larger C-terminal domain and a predominant middle kinase domain. In addition to these domains, a nuclear localization sequence has recently been identified [6]. The study aims to evaluate the expression and activity of glycogen synthase kinase 3 isoforms α/β (GSK3α/β) and to assess their oncogenic potential through a correlation with the expression of cyclin D1 and p53 in oral cancer
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