STUDIES ON THE ACTIVATION OF ONC GENES IN VIRUSES AND HUMAN TUMORS

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We have detected two transfectable transforming sequences following the screening of DNA from a human ovarian carcinoma cell line, OVCAR3, in the nude mouse tumor assay. The morphologically distinguishable transforming activities show differential response to the glucocorticoid dexamethasone (DEX) which abolishes our ability to detect morphological transformation induced by one of the two sequences. We have cloned a conserved alu + 10.5-kb fragment from this DEX-sensitive transformant. It represents the fusion of two normally unlinked sequences which apparently occurred during transfection. We have constructed a murine retrovirus (ME26) which carries avian gag, as well as v-myb and v-ets sequences derived from the avian erythroleukemia virus, E26. The virus replicates to high titer when rescued by replicating murine leukemia virus, and cells infected with the virus express a 140-Kd fusion protein which reacts with anti-avian gag and anti-ets antisera. The virus does not appear to transform NIH3T3 mouse embryo fibroblasts. We have transfected a bovine papillomavirus (BPV)-based construct which contains the human metallothionein gene and the murine sarcoma virus mos gene, either fused to human growth hormone (HGH) sequences under metallothionein control, or fused directly to a metallothionein promoter. Both constructs appears to transform mouse C127 cells and NIH3T3 cells. Very high levels of mos fusion protein can be detected in the presence of cadmium only in cells transformed by the HGH fusion construct.