Analysis of beta-catenin gene in gastric cancer cells

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Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer cells. We have recently demonstrated that the function of E-cadherin was completely abolished in HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins ; beta-catenin. In the present study, we firstly investigated beta-catenin gene expression in various human gastric cancer cells. It was revealed that a gastric carcinoma cell line KATO-III expressed the rearranged beta-catenin gene with amplification. Recently, it has been reported that beta-catenin binds to both APC and ErbB-2. Thus the function of E-cadherin system is supposed to affect the cell proliferation as well as cell-cell adhesion. We then transfected a wild-type beta-catenin gene expression vector into HSC-39 cells to examine the beta-catenin-mediated signal transduction. E-cadherin dependent cell-cell adhesiveness was recovered by the transfection of wild-type beta-catenin cDNA as revealed by cell compaction, cell-aggregation and immunofluorescence staining. In HSC-39beta cells, the cell proliferation, anchorageindependent growth and tumorigenecity were significantly reduced as comared with those of parental cells. Furthermore, the expressions of p21^<Cip1> and p27^<Kip1>, which inhibit the progression of cell cycle from G1 to S phase, were remarkably increased in HSC-39/beta. These results suggested that beta-catenin is involved in the cell cycle regulation as well as E-cadherin dependent cell-cell adhesion system.