Inoue H, Yamashita A, Hakura A
Department of Tumor Virology, Osaka University, Japan.
Virology. 1996 Nov 1;225(1):223-6. doi: 10.1006/viro.1996.0591.
G1/S transition of the cell cycle is blocked when cells are cultured without cell adhesion, even if nutrients and serum are present. Shift experiments involving transfer from adhesion to suspension cultures have revealed that cell adhesion in the early half of G1 phase is required for induction of DNA synthesis. We found that activation of p42/p44 mitogen-activated protein (MAP) kinases, one of the earliest responses induced by serum stimulation, was also dependent on cell adhesion in rat F2408 and mouse Swiss3T3 fibroblast cell lines, suggesting that MAP kinase activation is a critical step in adhesion-dependent G1 progression. F2408 cell lines transformed by the v-src, v-K-ras, and v-mos oncogenes showed constitutively high MAP kinase activity, even in the absence of serum and cell adhesion, while both serum stimulation and cell adhesion were necessary to induce intensive activation of MAP kinase in a F2408 cell line transformed by the E6 and E7 genes of human papillomavirus type 16, as well as in untransformed F2408.
即使存在营养物质和血清，当细胞在无细胞黏附的情况下培养时，细胞周期的G1/S转换也会被阻断。涉及从黏附培养转移至悬浮培养的转换实验表明，G1期前半段的细胞黏附是诱导DNA合成所必需的。我们发现，p42/p44丝裂原活化蛋白（MAP）激酶的激活是血清刺激诱导的最早反应之一，在大鼠F2408和小鼠Swiss3T3成纤维细胞系中，其激活也依赖于细胞黏附，这表明MAP激酶激活是黏附依赖性G1期进展中的关键步骤。由v-src、v-K-ras和v-mos癌基因转化的F2408细胞系即使在无血清和细胞黏附的情况下也表现出组成性的高MAP激酶活性，而在由人乳头瘤病毒16型的E6和E7基因转化的F2408细胞系以及未转化的F2408中，血清刺激和细胞黏附都是诱导MAP激酶强烈激活所必需的。
