Modulation of Cyclin D1 Expression by Integrin Signals in Oral Squamous Carcinoma Cells

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Cyclin D1 overexpression is frequently detected in oral squamous cell carcinomas (OSCC) and it is closely associated with the survival of OSCC patients. We examined cyclin D1 gene amplification with a panel of OSCC cell lines by the differential PCR technique. Any OSCC cell lines examined, however, did not show gene amplification of cyclin D1. Then, the expression of phosphorylated GSK-3β was examined by Western blotting, and was compared with cyclin D1 expression in OSCC cells. Interestingly, the expression of phosphorylated GSK-3β was reversely correlated with cyclin D1 expression, suggesting that lack of phosphorylated GSK-3β causes the intracellular accumulation of cyclin D1 in OSCC cells.Next, we tested cyclin D1 expression in various culture conditions, such as culturing with 10% FBS-containing medium or serum-free medium, as monolayer culture cells or multicellular aggregates (MCA), and on specific extracellular matrix proteins-coated surfaces or non-coated surface, and we found no differences in cyclin D1 level under these culture conditions. Furthermore, localizations of cyclin D1, GSK-3, Akt and Erk were investigated in monolayer cells and MCAs by immunofluorescent stainings. Results showed diffuse positive reactions without any differences between these proteins and between both the culture conditions.In this project, we could not present definite evidence of involvement of integrin signals in cyclin D1 expression in OSCC cell lines. Further studies are required to clarify the mechanism of modulation of GSK-3β functionality in OSCC.