Retrovirus-based vectors are ideally suited for the introduction of genetic information into mammalian cells, both in culture and in vivo. If expression of genes introduced with these vectors could be made conditional, their usefulness would be considerably enhanced. Regulation of expression from a glucocorticoid-induced promoter would be an attractive candidate, since most cell types contain functional glucocorticoid receptors. We have shown previously that expression of the v-Ha-ras oncogene can be made conditional when driven from the glucocorticoid responsive mouse mammary tumor virus promoter and that the transformed state of cells transfected with these fusions also is dependent on the presence of hormone. A preliminary series of vectors have been constructed with the MMTV v-Ha-ras cassette embedded in a retroviral backbone based on replication-competent murine leukemia virus, both in the parallel and anti-parallel transcriptional orientation. The neomycin resistance gene driven from the MuLV promoter has been included to provide selection independent of ras transformation. We find that hormone-dependent expression of the ras oncogene is observed with both orientations of the MMTV v-Ha-ras cassette. These experiments show, in principle, that a retrovirus-based vector can be developed which permits introduction of a given gene into cells with selection expression independent of the gene, and with subssequent expression of the gene subject to glucocorticoid regulation.
