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

• Published in: Experimental cell research Vol. 309; no. 2; pp. 397 - 409
• Main Authors: Yoshida, Ken-ichi, Kanaoka, Shigeru, Takai, Tetsunari, Uezato, Tadayoshi, Miura, Naoyuki, Kajimura, Masayoshi, Hishida, Akira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2005; Elsevier BV
• Subjects: Animals; Cattle; Cell Communication - physiology; Cell Line, Tumor; Culture Media; Cytoplasm - enzymology; Cytoplasm - metabolism; Epidermal growth factor (EGF); Epidermal Growth Factor - physiology; Gastric cancer; Humans; Immunohistochemistry; Membrane Proteins - metabolism; Occludin; Phosphoproteins - metabolism; Protein kinase C (PKC); Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Stomach Neoplasms - enzymology; Tight junction; Tight Junctions - metabolism; ZO-1; Zonula Occludens-1 Protein; Tight junction; ZO-1; Gastric cancer; Epidermal growth factor (EGF); Occludin; Protein kinase C (PKC)
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2005.06.019

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.