The segment polarity gene wingless is the Drosophila ortholog of mouse Wnt-1, a proto-oncogene capable of causing transformation of mammary epithelial cells. These two genes presently represent the best studied members of the Wnt gene family. To evaluate the functional significance of the sequence conservation between wingless and Wnt-1, we have examined the effects of expressing the Drosophila gene in mouse mammary epithelial cell lines, wingless induced morphological transformation, focus formation, and mitogenesis in confluent cultures of these cells, with resulting phenotypes comparable to those obtained with mouse Wnt-1. In addition, RAC311c mammary cells expressing wingless were tumorigenic, indicating that the Drosophila gene is capable of inducing full neoplastic transformation. In cell co-culture experiments, wingless caused transformation via a paracrine mechanism, consistent with the extracellular location of its product and its proposed mechanism of action in Drosophila embryos. Our results indicate that wingless is functionally analogous to Wnt-1 in these mammary cell transformation assays and imply a striking conservation in the properties of the two gene products and their mechanisms of action.

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