title: Regulation of cellular invasion and matrix metalloproteinase activity in HepG2 cell by connexin 26 transfection.
abstract: We previously reported that connexin (Cx) 26 expression is involved in negative growth control of HepG2 cells established from a human hepatoma. We also found that induction of E-cadherin and subsequent formation of a cell adhesion complex were induced in HepG2 cells by Cx 26 expression. To examine the exact role of Cx 26-induced E-cadherin junctions in regulating appearance of malignant phenotypes of HepG2 cells, we expressed a Cx 26 antisense oligodeoxynucleotide (AS-ODN) in an established HepG2 cell clone that has stable expression of Cx 26 genes. We investigated changes in the expression of E-cadherin, the localization of beta-catenin, and some malignant phenotypes of HepG2 clone after the suppression of Cx 26 expression by AS-ODN treatment. The AS-ODN treatment prevented the expression of Cx 26 and E-cadherin, and the localization of beta-catenin was changed from cytoplasmic membrane to the cytoplasm. In parallel, a morphological change from a monolayer of polygonal cells to multilayered colonies was induced by the treatment, indicating a change of a malignant phenotype of HepG2 cells. The activity of matrix metalloproteinase 9 (MMP-9) was elevated by the AS-ODN treatment. A concomitant increase in invasiveness of the Cx 26-expressing cells by the treatment was also observed in an in vitro assay with Matrigel matrix. These results suggest that the induction of E-cadherin and formation of the cell adhesion complex by Cx 26 expression contribute to the reversal of some malignant phenotypes of HepG2 cells. Furthermore, the Cx 26-dependent expression of E-cadherin leads to reduction of the invasiveness of the cells through suppression of MMP-9 activity.
authors: Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
authors: T
authors: T
authors: Yano
authors: H
authors: H
authors: Yamasaki
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D017630:Connexins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004338:Drug Combinations; C000607044:Gjb2 protein, rat; D007797:Laminin; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; D015534:Trans-Activators; D051176:beta Catenin; C059485:matrigel; D000072259:Connexin 26; D003094:Collagen; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9