A SOLUBLE FORM OF WNT-1 PROTEIN WITH MITOGENIC ACTIVITY ON MAMMARY EPITHELIAL-CELLS

The proto-oncogene Wnt-1 plays an essential role in fetal brain develo pment and causes hyperplasia and tumorigenesis when activated ectopica lly in the mouse mammary gland. When expressed in certain mammary epit helial cell lines, the gene causes morphological transformation and ex cess cell proliferation at confluence. Like other members of the mamma lian Wnt family, Wnt-1 encodes secretory glycoproteins which have been detected in association with the extracellular matrix or cell surface but which have not previously been found in a soluble or biologically active form. We show here that conditioned medium harvested from a ma mmary cell line expressing Wnt-1 contains soluble Wnt-1 protein and in duces mitogenesis and transformation of mammary target cells. By immun odepletion of medium containing epitope-tagged Wnt-1, we show that at least 60% of this activity is specifically dependent on Wnt-1 protein. These results provide the first demonstration that a mammalian Wnt pr otein can act as a diffusible extracellular signaling factor.