GSK3? and CREB3 gene expression profiling in benign and malignant salivary gland tumors

Abstract

Background: Salivary gland tumors (SGT) are rare lesions with uncertain histopathology. One of the major signaling pathways that participate in the development of several tumors is protein kinase A. In this pathway, glycogen synthase kinase ? (GSK3?) and cAMP responsive element binding protein (CREB3) are two genes which are supposed to be down regulated in most human tumors. The expression level of the genes was evaluated in SGT to scrutinize their possible under expression in these tumors. Methods: Forty eight fresh tissue samples were obtained from patients with benign and malignant SGT, including pleomorphic adenoma, warthin's tumor, mucoepidermoid carcinoma (MEC), salivary duct carcinoma and carcinoma ex pleomorphic adenoma. Eight normal samples were used as controls. Quantitative real-time PCR was used to analyze the expression level of interest genes. Results: Data was analyzed by statistical methods. GSK3? was downregulate in all samples and all results were statistically significant (P<0.05). CREB3 did not show a significant decrease or increase in its mRNA expression, but the results were significant in MEC and salivary duct carcinoma. Conclusion: GSK3? down regulation has been reported in many human tumors. This gene stimulates CREB3, inducing cell proliferation and oncogenesis. Our findings showed GSK3? down regulation; however, CREB3 expression level was close to normal group. No association between CREB3 expression and inactivated GSK3? could be postulated in SGT.