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Publication : The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells.

First Author  Liu BY Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  12 Pages  4158-63
PubMed ID  15020770 Mgi Jnum  J:89233
Mgi Id  MGI:3039206 Doi  10.1073/pnas.0400699101
Citation  Liu BY, et al. (2004) The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc Natl Acad Sci U S A 101(12):4158-63
abstractText  Ectopic activation of the Wnt signaling pathway is highly oncogenic for many human tissues. Here, we show that ectopic Wnt signaling increases the effective stem cell activity in mouse mammary glands in vivo. Furthermore, Wnt effectors induce the accumulation of mouse mammary epithelial progenitors (assayed by Hoechst dye exclusion, a surrogate stem cell marker, side population cells) both in vivo and in vitro. The longevity of stem cells makes them good candidate tumor precursors, and we propose that Wnt-induced progenitor amplification is likely to be key to tumor initiation. In support of this notion, mammary glands from a tumor-resistant strain of mice (carrying a null mutation in syndecan-1) contain fewer side population cells. When this strain is crossed to mice that overexpress effectors of the beta-catenin/T cell factor Wnt pathway, the amplification of progenitors is reduced, together with all subsequent events of tumor development. We propose that the growth dynamic of the stem cell fraction is a major determinant of tumor susceptibility.
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