STUDIES ON THE ACTIVATION OF ONCOGENES IN VIRUSES AND HUMAN TUMORS

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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.