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Effects of tyrosine kinase inhibitor, erbstatin, on cell growth and growth-factor/receptor gene expression in human gastric carcinoma cells

✍ Scribed by Naoki Takekura; Wataru Yasui; Eikai Kyo; Kazuhiro Yoshida; Takashi Kameda; Yasuhiko Kitadai; Kaoru Abe; Kazuo Umezawa; Eiichi Tahara

Publisher
John Wiley and Sons
Year
1991
Tongue
French
Weight
571 KB
Volume
47
Category
Article
ISSN
0020-7136

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✦ Synopsis

The effect of tyrosine kinase inhibitor, erbstatin, on cell growth and mRNA expression of growth-factor/receptor system was examined in 6 human gastric-carcinoma cell lines. Erbstatin inhibited both EGF-induced and serum-stimulated cell growth of all 6 cell lines (TMK-I, MKN-I, -7, -28, -45, -74) in a dose-dependent manner. lH-thymidine incorporation by TMK-I cells was also suppressed by erbstatin. Erbstatin inhibited protein kinase activity of EGF receptor, p I 85ERes2 and ppbQ-= in TMK-I cells. The expression of mRNA of EGF receptor gene and ERBB-2 by TMK-I cells was not changed by erbstatin treatment, whereas that of c-src was slightly decreased. Interestingly, erbstatin decreased membrane-bound TGF-a precursor as measured by anti-TGF-a antibodybinding assay, although mRNA expression for TGF-a was not altered by erbstatin. Our findings suggest that erbstatin may act as a growth inhibitor for human gastric-carcinoma cells and may not only inhibit tyrosine kinase activities but also negatively modulate the post-transcriptional step of TGF-a expression.

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