Accession Number : ADA329512

Title :   WNT Proteins in Mammary Epithelial Cell Transformation.

Descriptive Note : Annual rept. 1 Jun 96-31 May 97,

Corporate Author : COLUMBIA UNIV NEW YORK

Personal Author(s) : Kitajewski, Jan

PDF Url : ADA329512

Report Date : JUL 1997

Pagination or Media Count : 74

Abstract : We have assessed the ability of Wnt-1, Wnt-2, Wnt-3, Wnt-3A, Wnt-4, Wnt-5A, Wnt-5B, Wnt-6, Wnt-7A, and Wnt-7B to transform mammary epithelial cells and found that Wnt-1, Wnt-2, Wnt-3 and Wnt-3A proteins transform mammary epithelial cells; Wnt-7A and Wnt-7B proteins partially transform; and Wnt-4, Wnt-5A, Wnt-5B, and Wnt-6 proteins does not affect mammary epithelial cells. Transformation correlated with Wnt-mediated increases in the cytosolic pool of beta-catenin. By generating chimeric Wnt proteins and Wnt-1 deletions we have defined regions of Wnt-1 that are critical for transformation potential, signal transduction and frzb association. We have demonstrated that a secreted protein, frzb, blocks Wnt signaling and that a cytosolic protein, fused, is a negative regulator of Wnt signaling in mammalian cells. Wnt-1 acts as a mitogen in cultured Rat-1 fibroblasts, allowing growth of cells in serum-free medium. Using the TAC-2 mammary epithelial cell line, we found that Wnt-1 induces branching morphogenesis of mammary epithelial cells and can act as a morphogen in this capacity.

Descriptors :   *CELLS(BIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, EPITHELIUM, PHASE TRANSFORMATIONS, CELLS, GROWTH(GENERAL), PROTEINS, REGULATORS, SIGNALS, GENES, TRANSDUCERS, WOMEN, MORPHOGENESIS.

Subject Categories : Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE