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

Abstract:

: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.

authors

Liu BY,McDermott SP,Khwaja SS,Alexander CM

doi

10.1073/pnas.0400699101

keywords:

subject

Has Abstract

pub_date

2004-03-23 00:00:00

pages

4158-63

issue

12

eissn

0027-8424

issn

1091-6490

pii

0400699101

journal_volume

101

pub_type

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