Effects of E-cadherin transfection on gene expression of a gallbladder carcinoma cell line: repression of MTS1/S100A4 gene expression.
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.
Kohya
Naohiko
N
Department of Surgery, Saga Medical School, Saga, Japan.
Kitajima
Yoshihiko
Y
Jiao
Wan
W
Miyazaki
Kohji
K
D000368:Aged; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin; D015993:Life Tables; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C059485:matrigel; C077591:S100A4 protein, human; D003094:Collagen