Nomura T, Ryoyama K, Okada G, Matano S, Nakamura S, Kameyama T
Department of Molecular Biology, School of Medicine, Kanazawa University.
Jpn J Cancer Res. 1992 Aug;83(8):851-8. doi: 10.1111/j.1349-7006.1992.tb01990.x.
The anti-proliferative effect of azatyrosine, a newly discovered antibiotic from Streptomyces, was examined in Balb/c-originated serum-free mouse embryo (SFME) cells and transformed ras/myc SFME cells which have activated human c-Ha-ras genes. Azatyrosine suppressed their growth in a concentration-dependent manner. Growth suppression in both cells was detectable within 2 days after culture with 250 micrograms/ml azatyrosine. Non-transformed SFME cells, however, regained rapid growth after 6 days even in the presence of azatyrosine, whereas ras/myc SFME cells did not recover from the suppression. Despite the growth inhibition of ras/myc SFME cells, expression of human ras in the cells was not inhibited by azatyrosine. Meanwhile, SFME cells have the ability to express glial fibrillary acidic protein (GFAP). This expression is induced by serum-supplemented medium, though the serum inhibits the growth of SFME cells. Azatyrosine did not induce GFAP in ras/myc SFME cells, but inhibited growth. Furthermore, azatyrosine did not induce GFAP in SFME cells, and had no effect upon the expression of GFAP induced by serum in these cells. These results suggest that azatyrosine inhibited the growth of ras/myc SFME cells through a mechanism independent of those involved in growth inhibition and induction of GFAP expression by serum in SFME cells.
对一种新发现的来自链霉菌的抗生素氮酪氨酸在源自Balb/c的无血清小鼠胚胎（SFME）细胞以及已激活人c-Ha-ras基因的转化型ras/myc SFME细胞中的抗增殖作用进行了检测。氮酪氨酸以浓度依赖的方式抑制它们的生长。在用250微克/毫升氮酪氨酸培养2天后，两种细胞中的生长抑制均可检测到。然而，即使存在氮酪氨酸，未转化的SFME细胞在6天后仍恢复快速生长，而ras/myc SFME细胞并未从抑制中恢复。尽管ras/myc SFME细胞的生长受到抑制，但细胞中人ras的表达并未被氮酪氨酸抑制。同时，SFME细胞具有表达胶质纤维酸性蛋白（GFAP）的能力。这种表达由补充血清的培养基诱导，尽管血清会抑制SFME细胞的生长。氮酪氨酸在ras/myc SFME细胞中未诱导GFAP表达，但抑制了生长。此外，氮酪氨酸在SFME细胞中未诱导GFAP表达，并且对血清在这些细胞中诱导的GFAP表达没有影响。这些结果表明，氮酪氨酸通过一种独立于SFME细胞中血清抑制生长和诱导GFAP表达所涉及机制的机制来抑制ras/myc SFME细胞的生长。
