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© The Rockefeller University Press,
0021-9525/2001//555 $5.00
The Journal of Cell Biology, Volume 153, Number 3,
, 2001 555-568
Original Article |
n89β-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland
cowinp01{at}med.nyu.edu
To investigate the role of β-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of β-catenin lacking the NH2-terminal 89 amino acids (
N89β-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that
N89β-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin
N89β-catenin mammary glands resemble those found in wild-type (wt) pregnant mice and inappropriately express cyclin D1 mRNA. In contrast to wt mammary glands, which resume a virgin appearance after cessation of lactation, transgenic mammary glands involute to a midpregnant status. All transgenic females develop multiple aggressive adenocarcinomas early in life. Surprisingly, the
N89β-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular,
N89β-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.
Key Words: β-catenin mammary gland cyclin D1 cadherin Wnt
© 2001 The Rockefeller University Press
Alexandra Imbert and Rachel Eelkema contributed equally to this work and should be considered co-first authors.Abbreviations used in this paper: Lef, lymphoid enhancer factor; Tcf, T cell factor; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; wt, wild-type.
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