GROWTH MODULATION OF RAF ASSOCIATED TUMORS

从缺陷型逆转录病毒中鉴定v-raf-1癌基因 3611-MSV已经允许分离出一个新的原癌基因家族。这个 V-raf的活性同源基因c-raf-1位于染色体上的p25位 3在人类中，在各种肿瘤中经常发生改变的部位， 包括小细胞肺癌。此外，转换版本的 C-RAF-1在人类胃癌和胶质母细胞瘤中已被发现。 C-raf-1mRNA和蛋白在人肺癌细胞系中的表达 发生的水平高于NIH 3T3细胞的水平 经c-RAF MSV转化。研究RAF在肺癌发生中的作用 在体内，我们已经开发出一种动物模型，90%的新生小鼠 经胎盘用乙基亚硝脲治疗，出生时用 丁基羟基甲苯在5-14岁内发展为肺癌和淋巴瘤 几周。C-raf-1在肿瘤和已建立的细胞系中的高表达 经Northern印迹和免疫印迹分析鉴定。准备好的DNA 从肺癌和淋巴瘤向NIH3T3细胞转化为 通过DNA转染法测定。激活转化的本质 目前正在对DNA进行检测。此外，我们现在已经定义了条件 利用生长调节剂和激素进行差异性抑制 体外转化的RAF对照细胞系，但不是未转化的对照细胞系。这些 这些疗法现在正在我们的动物模型系统中进行测试， 用纯化的RAF蛋白进行疫苗接种实验，以检查他们的 对这些肿瘤发展有潜在的抑制作用。

The identification of the v-raf-1 oncogene from the defective retrovirus 3611-MSV has allowed the isolation of a new family of proto-oncogenes. The active homolog of v-raf, c-raf-1, is located at position p25 on chromosome 3 in man, a site that is frequently altered in a variety of neoplasia, including small cell lung carcinoma. Moreover, transforming versions of c-raf-1 have been identified in human stomach cancer and glioblastoma. Expression of c-raf-1 mRNA and protein in human lung carcinoma cell lines occurs at levels that are in excess of those found in NIH 3T3 cells transformed by c-raf MSV. To study the role of raf in lung carcinogenesis in vivo, we have developed an animal model where 90% of newborn mice treated transplacentally with ethylnitrosourea and promoted at birth with butylated hydroxytoluene develop lung tumors and lymphomas within 5 to 14 weeks. High c-raf-1 expression in tumors and established cell lines has been determined by Northern blot and immunoblotting analyses. DNA prepared from both lung tumors and lymphomas is transforming for NIH 3T3 cells as determined by DNA-transfection. The nature of the activated transforming DNA is currently being examined. Moreover, we have now defined conditions using growth modulators and hormones for the differential inhibition of raf-transformed, but not untransformed, control cell lines in vitro. These regimens are now being tested in our animal model system, in conjunction with vaccination experiments using purified raf protein, to examine their potential inhibitory actions on the development of these tumors.