EXPRESSION AND TYROSINE PHOSPHORYLATION OF PHOSPHATIDYL-INOSITOL-3 KINASE IN HUMAN GASTRIC-CANCER CELLS - ITS CORRELATION WITH CELL-GROWTH
- HY XIAO
- Y NAGAI
- Y FUKUI
- K TAMIYAKOIZUMI
- H IWATA
- T WATANABE
- M HAMAGUCHI
Affiliations: 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.
- Published online on: February 1, 1995 https://doi.org/10.3892/ijo.6.2.405
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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.