Journal
JOURNAL OF CELL BIOLOGY
Volume 153, Issue 3, Pages 555-568Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.153.3.555
Keywords
beta-catenin; mammary gland; cyclin D1; cadherin; Wnt
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Funding
- NIGMS NIH HHS [GM47429, R01 GM047429] Funding Source: Medline
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To investigate the role of beta -catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of beta -catenin lacking the NH2-terminal 89 amino acids (Delta N89 beta -catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that Delta N89 beta -catenin induces precocious loburoalveolar development and differentiation in the mammary glands of both male and female mice. Virgin Delta N89 beta -catenin mammary glands resemble those found in wild-type (wt) pregnant mice and inappropriately express cyclin 191 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 N89 beta -catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, Delta N89 beta -catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effecters or modulators.
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