Kadohama T, Tsuji K, Ogawa K
Department of Pathology, Asahikawa Medical College, Japan.
Oncogene. 1994 Oct;9(10):2845-52.
Growth arrest after u.v. damage was investigated in C3H mouse primary cultured hepatocytes, spontaneously immortalized liver epithelial cells and their H-ras-transformed derivatives. All cells except for one of the transformed lines had the wild type p53 gene considered necessary for the G1-S checkpoint. Growth arrest and accumulation of p53 protein with an abnormally-extended half-life were observed after 8 J/m2 u.v. treatment in primary hepatocytes and immortalized cells, but the arrest was much less evident in H-ras-transformed cells, in spite of the presence of the wild type p53 gene and accumulation of p53. Thus, the signal transduction upstream of p53 in the p53-mediated G1-S checkpoint may be retained in these transformed cell lines, although its downstream signal transduction or a pathway totally independent of this system could be altered. The transformed cells showed a much wider distribution of chromosomal number as compared to normal and immortalized cells, indicating that progression from the immortal to transformed state is associated with chromosomal instability, together with much decrease in the cell cycle checkpoint function.
在C3H小鼠原代培养肝细胞、自发永生化肝上皮细胞及其H-ras转化衍生物中研究了紫外线损伤后的生长停滞情况。除了一个转化细胞系外，所有细胞都具有野生型p53基因，该基因被认为是G1-S期检查点所必需的。在原代肝细胞和永生化细胞中，8 J/m2紫外线处理后观察到生长停滞和p53蛋白积累，且其半衰期异常延长，但在H-ras转化细胞中，尽管存在野生型p53基因且p53有积累，生长停滞却不太明显。因此，在p53介导的G1-S期检查点中，p53上游的信号转导在这些转化细胞系中可能得以保留，尽管其下游信号转导或完全独立于该系统的一条途径可能发生了改变。与正常细胞和永生化细胞相比，转化细胞显示出更广泛的染色体数分布，这表明从永生化状态到转化状态的转变与染色体不稳定性相关，同时细胞周期检查点功能也大幅下降。
