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Published online 30 April 2001. doi:10.1083/jcb.153.3.555
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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

{Delta}n89β-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland



Alexandra Imberta, Rachel Eelkemaa, Sara Jordana, Helen Feinerb, and Pamela Cowina

a Department of Cell Biology and Department of Dermatology, New York University Medical School, New York, New York 10016
b Department of Pathology, New York University Medical School, New York, New York 10016
Department of Cell Biology, New York University Medical School, 550 First Ave., New York, NY 10016.(212) 263-8139/8752(212) 263-8715

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 ({Delta}N89β-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that {Delta}N89β-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin {Delta}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 {Delta}N89β-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, {Delta}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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