Original Article

N89ß-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland

Correspondence to: Pamela Cowin, Department of Cell Biology, New York University Medical School, 550 First Ave., New York, NY 10016. Tel:(212) 263-8715 Fax:(212) 263-8139/8752 E-mail:cowinp01{at}med.nyu.edu.

To investigate the role of ß-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of ß-catenin lacking the NH₂-terminal 89 amino acids (N89ß-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that N89ß-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin N89ß-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 N89ß-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, N89ß-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.

Key Words: ß-catenin, mammary gland, cyclin D1, cadherin, Wnt

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