The oncogenic potential of deregulated homeobox genes.

Homeobox genes encode DNA-binding proteins that regulate gene expression during embryonic development. Deregulation of homeobox gene expression has been invoked as the molecular basis of a number of leukemias. We now demonstrate, using in vitro and in vivo transformation assays, that the overexpression of homeobox genes is the basis for transformation and tumorigenesis. Thus, clustered homeobox genes related to Drosophila Hom genes (Hoxa-7, Hoxa-5, Hoxa-1, Hoxb-7, and Hoxc-8) as well as the homeobox genes Evx-1 and Cdx-1 constitute a new family of nuclear protooncogenes. This finding suggests that many homeobox genes regulating embryogenesis can--if deregulated--also contribute to tumorigenesis.