A soluble form of Wnt-1 protein with mitogenic activity on mammary epithelial cells

Author:

Bradley R S1,Brown A M1

Affiliation:

1. Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021, USA.

Abstract

The proto-oncogene Wnt-1 plays an essential role in fetal brain development and causes hyperplasia and tumorigenesis when activated ectopically in the mouse mammary gland. When expressed in certain mammary epithelial cell lines, the gene causes morphological transformation and excess cell proliferation at confluence. Like other members of the mammalian 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 mammary cell line expressing Wnt-1 contains soluble Wnt-1 protein and induces mitogenesis and transformation of mammary target cells. By immunodepletion 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 protein can act as a diffusible extracellular signaling factor.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Reference57 articles.

1. The biochemical properties and transforming potential of human Wnt-2 are similar to Wnt-1;Blasband A.;Oncogene,1992

2. Alterations of the growth characteristics of the fibroblast cell line C3H 10T1/2 by members of the Wnt gene family;Bradbury J. M.;Oncogene,1994

3. .Bradley R. S. Unpublished data.

4. The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix;Bradley R. S.;EMBO J.,1990

5. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin levels and an increase in cell-cell adhesion;Bradley R. S.;J. Cell Biol.,1993

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