Moon H S, Choi E A, Park H Y, Choi J Y, Chung H W, Kim J I, Park W I
Department of Obstetrics and Gynecology, Ewha Womans University, Seoul, 158-710, Korea.
Gynecol Oncol. 2001 Jun;81(3):355-9. doi: 10.1006/gyno.2001.6163.
The cadherin/catenin adhesion complex is fundamentally involved in epithelial cancer invasion and metastasis. Much evidence suggesting that epidermal growth factor (EGF) induced the scattering and invasion of cancer cells, probably by affecting E-cadherin function, has been reported. The present study aimed to confirm the hypothesis that EGF/epidermal growth factor receptor (EGFR) was related with the E-cadherin adhesion system in cervical cancer cells and that EGF might induce tyrosine phosphorylation of beta- and gamma-catenin.
Cervical cancer cells were treated for different time durations with 30 ng/ml of EGF. Alteration of the cell morphology was examined by light microscopy and the expression of E-cadherin, beta-catenin, gamma-catenin, EGFR, and activated EGFR was assayed using Western blotting. Tyrosine phosphorylation of beta- and gamma-catenin was also examined using immunoprecipitation.
E-cadherin and EGFR were expressed in CaSki, HT-3, and ME-180 cell lines, which showed epithelial contact growth. The expression of E-cadherin and beta- and gamma-catenin did not change after treatment with EGF. The expression of EGFR decreased and activated EGFR expression increased in 30 min and then decreased subsequently. The simultaneous expression of activated EGFR and tyrosine phosphorylation of beta- and gamma-catenin was found.
EGF-induced scattering of the E-cadherin-positive cervical cancer cells might be the result of tyrosine phosphorylation of the beta- and gamma-catenin. Phosphorylation of the beta- and gamma-catenin may hamper the adhesive function of the E-cadherin-catenin complex.
钙黏蛋白/连环蛋白黏附复合体在上皮癌侵袭和转移中起根本作用。已有许多证据表明，表皮生长因子（EGF）可能通过影响E-钙黏蛋白功能诱导癌细胞的分散和侵袭。本研究旨在证实以下假设：EGF/表皮生长因子受体（EGFR）与宫颈癌细胞中的E-钙黏蛋白黏附系统相关，且EGF可能诱导β-连环蛋白和γ-连环蛋白的酪氨酸磷酸化。
用30 ng/ml的EGF处理宫颈癌细胞不同时间。通过光学显微镜检查细胞形态的改变，并用蛋白质免疫印迹法检测E-钙黏蛋白、β-连环蛋白、γ-连环蛋白、EGFR和活化EGFR的表达。还使用免疫沉淀法检测β-连环蛋白和γ-连环蛋白的酪氨酸磷酸化。
E-钙黏蛋白和EGFR在CaSki、HT-3和ME-180细胞系中表达，这些细胞系表现出上皮接触生长。用EGF处理后，E-钙黏蛋白、β-连环蛋白和γ-连环蛋白的表达没有变化。EGFR的表达在30分钟时下降，活化EGFR的表达增加，随后下降。发现活化EGFR与β-连环蛋白和γ-连环蛋白的酪氨酸磷酸化同时表达。
EGF诱导的E-钙黏蛋白阳性宫颈癌细胞的分散可能是β-连环蛋白和γ-连环蛋白酪氨酸磷酸化的结果。β-连环蛋白和γ-连环蛋白的磷酸化可能会阻碍E-钙黏蛋白-连环蛋白复合体的黏附功能。
