STUDIES ON THE ACTIVATION OF ONCOGENES IN VIRUSES AND HUMAN TUMORS

我们已经分析了部分OVC癌基因的DNA序列， DNA转染过程中激活的人转化序列和 来源于人卵巢癌细胞系OVCAR-3。 该序列与GenBank中的序列比较 数据库显示没有显著的同源性，这表明， 与之前的杂交数据一致，OVC代表着一种 ？以前未确定的人类致癌基因。PolyA+RNA的分析 从几个正常和转化的人类细胞株中发现 OVC序列在OVCAR-3亲本细胞系中表达， 另外三例人类腺癌。 我们之前已经证明，对小鼠成纤维细胞的治疗 衣霉素，一种糖基化抑制剂，使它们变得易感 对RD114猫内源性病毒及其伪型的感染。 我们现在已经证明了其他几种糖基化抑制剂， 它们在糖基化途径的不同点起作用，也 也有类似的效果。此外，小鼠淋巴样细胞还表现出 当暴露于衣霉素时，具有类似的特性。这表明 这可能代表了小鼠细胞的一个共同特征。 我们已经测试了来自两个细胞系的细胞DNA的能力 来自甲基胆蒽诱导的小鼠纤维肉瘤(TN-10)，以及 它们表现出不同的转移潜能，以转化NIH3T3 细胞。在高转染率下可诱导形成病灶 效率，转化的细胞已经获得了 在没有血清或蛋白质生长因子的情况下生长。不是 检测到几个特征良好的癌基因重排 在转基因细胞中，但病灶似乎包含扩增的拷贝 小鼠K-ras癌基因。

We have analyzed the DNA sequence of a portion of the ovc oncogene, a human transforming sequence activated during DNA transfection and derived from the human ovarian carcinoma cell line, OVCAR-3. Comparison of this sequence with sequences contained in the GenBank data base reveals no significant homologies, suggesting that, consistent with previous hybridization data, ovc represents a ?previously unidentified human oncogene. Analysis of poly-A+ RNA from several normal and transformed human cell lines indicates that ovc sequences are expressed in the OVCAR-3 parent cell line and three other human adenocarcinomas. We had previously shown that treatment of mouse fibroblasts with tunicamycin, a glycosylation inhibitor, renders them susceptible to infection by RD114 cat endogenous virus and its pseudotypes. We have now shown that several other inhibitors of glycosylation, which act at different points along the glycosylation pathway, also have a similar effect. In addition, mouse lymphoid cells exhibit similar properties when exposed to tunicamycin. This suggests that this may represent a common feature of mouse cells. We have tested the ability of cell DNA from two cell lines derived from a methylcholanthrene-induced mouse fibrosarcoma (TN-10), and which exhibit differing metastatic potentials, to transform NIH 3T3 cells. Foci are induced following transfection at high efficiencies, and transformed cells have acquired the ability to grow in the absence of serum or protein growth factors. No rearrangements of several well-characterized oncogenes are detected in transfected cells, but foci appear to contain amplified copies of the murine K-ras oncogene.