EGF rapidly translocates tight junction proteins from the cytoplasm to the cell-cell contact via protein kinase C activation in TMK-1 gastric cancer cells.
EGF rapidly translocates tight junction proteins from the cytoplasm to the cell-cell contact via protein kinase C activation in TMK-1 gastric cancer cells.
复制标题
DOI：
10.1016/j.yexcr.2005.06.019
复制
发表时间：
2005-10
影响因子：
3.7
通讯作者：
Ken-ichi Yoshida;S. Kanaoka;T. Takai;T. Uezato;N. Miura;M. Kajimura;A. Hishida
中科院分区：
文献类型：
--
作者：
Ken-ichi Yoshida;S. Kanaoka;T. Takai;T. Uezato;N. Miura;M. Kajimura;A. Hishida
在包括胃癌在内的癌细胞中，紧密连接通常被破坏。据报道，多种生长因子影响紧密连接相关蛋白（如ZO-1和occludin）的定位。我们研究了胃癌中经常过度表达的生长因子表皮生长因子（EGF）和胎牛血清（FBS）对胃癌细胞系ZO-1和occludin定位的影响。在低分化胃癌细胞系TMK-1中，免疫组化显示ZO-1和occludin主要定位于细胞质，尽管在细胞-细胞接触处也有少量表达。当培养基替换为含有10% FBS的新鲜培养基时，ZO-1和occludin迅速从细胞质转移到细胞-细胞接触处。在EGF暴露中也观察到类似的效果。FBS或EGF诱导的这些效应在蛋白激酶C （PKC）抑制剂calphostin C和双吲哚酰马来酰亚胺I存在时减弱，但在PKC抑制剂Gö6976、PD98059 （MAPK抑制剂）、LY294002 （PI3激酶抑制剂）或KT5720（蛋白激酶A抑制剂）存在时则不减弱。这些结果表明，包括EGF在内的血清源性因子可以通过TMK-1胃癌细胞中的蛋白激酶C信号通路快速改变ZO-1和occludin的定位。
Tight junctions are commonly disrupted in cancer cells, including gastric cancer. Various growth factors have been reported to affect the localization of tight junction-associated proteins such as ZO-1 and occludin. We investigated the effect of epidermal growth factor (EGF), a growth factor that is often overexpressed in gastric cancer, and fetal bovine serum (FBS) on the localization of ZO-1 and occludin in a gastric cancer cell line. In the poorly differentiated gastric cancer cell line TMK-1, immunohistochemistry demonstrated that ZO-1 and occludin were predominantly localized to the cytoplasm, although there was some weak expression at the cell–cell contact. When the medium was replaced with fresh medium containing 10% FBS, ZO-1 and occludin were rapidly translocated from the cytosol to the cell–cell contact. A similar effect was seen in EGF exposure. These effects induced by FBS or EGF were attenuated in the presence of protein kinase C (PKC) inhibitors calphostin C and bisindolylmaleimide I, but not another PKC inhibitor Gö6976, PD98059 (MAPK inhibitor), LY294002 (PI3 kinase inhibitor) or KT5720 (protein kinase A inhibitor). These results suggest that serum-derived factors, including EGF, can rapidly alter the localization of ZO-1 and occludin via a protein kinase C signaling pathway in TMK-1 gastric cancer cells.