title: Expression and tyrosine phosphorylation of phosphatidyl-inositol-3 kinase in human gastric-cancer cells - its correlation with cell-growth.
abstract: To reveal the signaling pathway leading to oncogenecity of human cancer cells, we examined the expression and tyrosine-phosphorylation of phosphatidylinositol (PI)-3 kinase in cancer cell lines. Of the 14 cell lines examined, two poorly differentiated human gastric cancer cell lines, NUGC-4 and MKN-45, which were previously found to have aberrant elevation of tyrosine phosphorylation showed elevated levels of PI-3 kinase 85-kDa subunit expression. In these cells, tyrosine-phosphorylation and overall activity of PI-3 kinase were apparently elevated, compared with normal human fibroblasts and another well differentiated gastric cancer cell line, MKN-28. Treatment of these cells with tyrosine kinase inhibitor, genistein, strongly suppressed the PI-3 kinase activity. Furthermore, wortmannin, a potent inhibitor of PI-3 kinase, strongly suppressed the growth of these gastric cancer cells. These results suggest that the growth signaling via tyrosine phosphorylation is required for the activation of PI-3 kinase in NUGC4 and MKN-45, and that this activation plays an important role in oncogenic growth of these cells. However, these two cell lines showed different responses of PI-3 kinase to acid-treatment and tyrosine kinase inhibitors. In MKN-45, activation of PI-3 kinase appeared to be constitutive, and could be relevant to the oncogenic nature of the cell line.
authors.affiliation: NAGOYA UNIV,SCH MED,DIS MECHANISM & CONTROL RES INST,SHOWA KU,NAGOYA,AICHI 466,JAPAN. UNIV TOKYO,INST MED SCI,MINATO KU,TOKYO 108,JAPAN. UNIV TOKYO,FAC AGR,BIOCHEM LAB,BUNKYO KU,TOKYO 113,JAPAN. FUJITA HLTH UNIV,SCH MED,HISAI 4241,JAPAN.
authors.forename: H
authors.initials: H
authors.lastname: Xiao
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.forename: Y
authors.initials: Y
authors.lastname: Fukui
authors.forename: K
authors.initials: K
authors.lastname: Tamiyakoizumi
authors.forename: H
authors.initials: H
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi