Yanagihara K, Ciardiello F, Talbot N, McGeady M L, Cooper H, Benade L, Salomon D S, Bassin R H
Laboratory of Tumor Immunology and Biology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Oncogene. 1990 Aug;5(8):1179-86.
A new class of nontransformed revertant cells has been isolated from the ras-transformed cell line DT using cis-4-hydroxy-L-proline (CHP) as a selective agent. The new revertants, CHP 9CJ and CHP CB4, each contain two copies of the v-Ki-ras gene, elevated levels of phosphorylated p21ras protein, and rescuable transforming virus, indicating that the revertant phenotype observed in these cells does not result from inactivation of v-Ki-ras or inhibition of its expression. Both CHP 9CJ and CHP CB4 revertants show a greatly reduced ability to form colonies in soft agar and to produce tumors in syngeneic mice. CHP 9CJ cells are resistant to retransformation by ras and by additional oncogenes that do not encode tyrosine kinases. A comparison of oncogene resistance patterns in these CHP-derived revertants with those from our original ouabain-derived revertants fos C-11 and F-2 indicates that oncogenes may be divided into four general groups. Oncogenes that encode proteins structurally related to p21ras comprise the first group. The second group contains only tyrosine kinase-encoding oncogenes. The third group is composed of 'nuclear', e.g. fos, and 'cytoplasmic' serine-threonine-encoding oncogenes such as mos and raf. The fourth group contains the oncogenes sis and fms.
利用顺式-4-羟基-L-脯氨酸（CHP）作为选择剂，从经ras转化的细胞系DT中分离出一类新的未转化回复细胞。新的回复细胞CHP 9CJ和CHP CB4各自含有两个v-Ki-ras基因拷贝、磷酸化p21ras蛋白水平升高以及可拯救的转化病毒，这表明在这些细胞中观察到的回复表型并非源于v-Ki-ras的失活或其表达的抑制。CHP 9CJ和CHP CB4回复细胞在软琼脂中形成集落以及在同基因小鼠中产生肿瘤的能力都大大降低。CHP 9CJ细胞对ras和其他不编码酪氨酸激酶的癌基因的再转化具有抗性。将这些源自CHP的回复细胞中的癌基因抗性模式与我们最初源自哇巴因的回复细胞fos C-11和F-2的模式进行比较，表明癌基因可分为四大类。编码与p21ras结构相关蛋白质的癌基因构成第一类。第二类仅包含编码酪氨酸激酶的癌基因。第三类由“核”癌基因（如fos）和“胞质”丝氨酸-苏氨酸编码癌基因（如mos和raf）组成。第四类包含癌基因sis和fms。
