Expression of the vav oncogene in somatic cell hybrids

The vav oncogene is expressed primarily in tissues of hematopoietic origin. While much effort has been focused on determining the role of vav in various signal transduction pathways, little is known about the mechanism by which vav is regulated in a tissue-selective manner. This issue was examined by developing somatic cell hybrids between human U937 cells, which express vav, and mouse Balb/c 3T3 cells, which do not. If vav is primarily regulated by the presence of positive acting transcription factors, then vav expression should be maintained in hybrid cells. In contrast, if the regulation of vav is primarily negative in nature, then vav expression should be extinguished in most of the somatic cell hybrids. Of the hybrid cells that were obtained, 64% were positive by reverse transcriptase-polymerase chain reaction for the expression of the vav oncogene. Differences in the pattern of restriction enzyme cleavage sites between the mouse and human PCR products were used to determine that 6 of 11 of the positive clones expressed the normally dormant mouse gene. The other positive clones were found to express the human vav gene. In all cases, the hybrid cells preferentially retained the chromosomes and the cellular morphological appearance of the mouse Balb/c 3T3 fusion partner, which does not express the vav oncogene. Since vav is able to be transiently expressed by hybrid cells with a predominately mouse phenotype, these results support the hypothesis that vav is regulated primarily by the presence of transactivating factors which stimulate transcription, rather than by a gene silencing mechanism.