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

为了研究接触抑制的机制，我们从亲本非粘附性HSC 39胃癌细胞系中克隆了一个粘附亚系HSC 39 Ad，该细胞系β-连环蛋白基因缺失（Mol Cell Biol 1995 Mar：15（3）：1175-81）。该亚系在体外和体内生长均比亲本细胞慢。E-cadherin中和抗体（HECD 1）使HSC 39 Ad细胞失去粘附特性，导致细胞生长速度加快，p21/WAF 1和Rb蛋白表达下降。而γ-catenin反义寡核苷酸在HSC 39 Ad中的表达量是HSC 39细胞的2倍。另一方面，用HECD 1处理HSC 39 Ad细胞引起小GTP结合蛋白Rho的活化。Rho抑制剂C3可恢复HECD 1诱导的HSC 39 Ad细胞生长速度的提高和p21/WAF 1表达的降低。这些结果表明，β-catenin与E-cadherin结合后，通过Rho将信号传导至p21/WAF 1，导致HSC 39细胞的接触抑制。

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.