Effects of E‐cadherin transfection on gene expression of a gallbladder carcinoma cell line: Repression of MTS1/S100A4 gene expression

Abstract

E-cadherin is important in cell-to-cell adhesion and controls cell polarity and tissue morphology. Loss of E-cadherin expression occurs in various human tumors and is the first step in cancer invasion and metastasis. We demonstrate that the exogenous expression of E-cadherin transfected into G-415 GB cells not only increases cell-to-cell adhesion but also reduces in vitro cell proliferation, motility and invasion. Our aim was to determine what genes are most affected by the exogenous expression of E-cadherin in GB cancer cells. We analyzed gene expression pertaining to cell proliferation, motility and invasion. Conventional RT-PCR was performed for these genes; quantitative RT-PCR was carried out on genes exhibiting altered expression. Conventional RT-PCR revealed that E-cadherin transfection suppressed expression of mts1 mRNA and increased that of c-myc and MT1-MMP. In quantitative RT-PCR analysis, levels of c-myc and MT1-MMP mRNA were elevated by to 2.56- and 2.22-fold, respectively, in the E-cadherin transfectant, whereas mts-1 was 7.14-fold suppressed compared to parental cells. These results indicated that expression of mts1 mRNA was most affected by E-cadherin transfection. Immunocytochemical analysis of transfectant and parental cells demonstrated an inverse correlation in E-cadherin and mts1 expression. Immunohistochemical analysis of 37 GB cancer specimens confirmed this observation in vivo. Loss of E-cadherin expression followed by expression of the mts1 gene may be an important event for increasing cell proliferation, motility and invasion activity in the progression of GB cancer.