Regulation of cellular invasion and matrix metalloproteinase activity in HepG2 cell by connexin 26 transfection

✍ Scribed by Tomohiro Yano; Hiroshi Yamasaki

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 427 KB
• Volume: 31
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.1045

✦ Synopsis

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 C × 26 expression. To examine the exact role of C × 26‐induced E‐cadherin junctions in regulating appearance of malignant phenotypes of HepG2 cells, we expressed a C × 26 antisense oligodeoxynucleotide (AS‐ODN) in an established HepG2 cell clone that has stable expression of C × 26 genes. We investigated changes in the expression of E‐cadherin, the localization of β‐catenin, and some malignant phenotypes of HepG2 clone after the suppression of C × 26 expression by AS‐ODN treatment. The AS‐ODN treatment prevented the expression of C × 26 and E‐cadherin, and the localization of β‐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 C × 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 C × 26 expression contribute to the reversal of some malignant phenotypes of HepG2 cells. Furthermore, the C × 26‐dependent expression of E‐cadherin leads to reduction of the invasiveness of the cells through suppression of MMP‐9 activity. © 2001 Wiley‐Liss, Inc.