Nose K, Itami M, Satake M, Ito Y, Kuroki T
Department of Cancer Cell Research, University of Tokyo, Japan.
Mol Carcinog. 1989;2(4):208-16. doi: 10.1002/mc.2940020407.
Proto-oncogene c-fos is induced by many types of cellular stimuli, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth factor (EGF), serum (fetal bovine), calcium ionophore A23187, and dibutyryl cAMP (But2cAMP). In this study, c-fos induction was abolished in ras-transformed mouse osteoblast cells (MC3T3). Transformants of MC3T3 were isolated after transfection with Ki or Ha murine sarcoma virus DNA. All Ki- or Ha-ras transformed MC3T3 clones examined showed exceedingly low levels of c-fos induction by all inducers, as determined by the change in amounts of c-fos mRNA or its product. Induction of other TPA-responsive genes, such as metallothionein, was not altered in some ras-transformed cells; c-myc and c-jun expression was constitutively high in all the ras-transformed clones. Nuclear extracts and gel shift assay showed that the binding activity to c-fos enhancer element (serum response element) was altered in ras-transformed cells. These results indicate that transformation with ras oncogene induces modification of c-fos enhancer binding factors and that this modification is one cause for the decrease in c-fos induction.
原癌基因c-fos可被多种细胞刺激诱导，如12-O-十四烷酰佛波醇-13-乙酸酯（TPA）、表皮生长因子（EGF）、血清（胎牛血清）、钙离子载体A23187和二丁酰环磷腺苷（But2cAMP）。在本研究中，在ras转化的小鼠成骨细胞（MC3T3）中，c-fos的诱导被消除。用Ki或Ha小鼠肉瘤病毒DNA转染后，分离出MC3T3的转化体。通过c-fos mRNA或其产物量的变化测定，所有检测的Ki-或Ha-ras转化的MC3T3克隆对所有诱导剂的c-fos诱导水平都极低。在一些ras转化细胞中，其他TPA反应性基因（如金属硫蛋白）的诱导没有改变；在所有ras转化克隆中，c-myc和c-jun的表达持续处于高水平。核提取物和凝胶迁移试验表明，在ras转化细胞中，与c-fos增强子元件（血清反应元件）的结合活性发生了改变。这些结果表明，ras癌基因转化诱导了c-fos增强子结合因子的修饰，并且这种修饰是c-fos诱导减少的原因之一。
