Analysis of E-cadherin-Dependent Contact Inhibition in Gastric Cancer Cell Line

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To investigate the mechanism of contact inhibition, we cloned an adhesive subline HSC39Ad from parental non-adhesive HSC39 gastric cancer cell line, which has a deletion in the β-catenin gene (Mol Cell Biol 1995 Mar : 15(3) : 1175-81). This subline grew slower than the parental cells in vitro and in vivo. The neutralizing antibody of E-cadherin (HECD1) caused the lost of adhesive character of HSC39Ad cells, resulting in the enhancement of growth rate and the decrement of the expression of both p21/WAF1 and Rb in the dephosphorylated form. The same results were obtained by the specific antisense oligonucleotide against γ-catenin, which was expressed in HSC39Ad two-times higher than HSC39 cells. On the other hand, the treatment of HSC39Ad cells with HECD1 caused the activation of the small GTP-binding protein Rho. Further, C3, the inhibitor of Rho, restored both the enhancement of growth rate and the decrement of the expression of p21/WAF1 induced by HECD1 in HSC39 Ad cells. These results indicate that β-catenin bound with E-cadherin causes the signal transduction via Rho to p21/WAF1, resulting in the contact inhibition of HSC39 cells.