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PMID: 11331306 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.

The Journal of cell biology ·Vol. 153 ·No. 3 ·2001-04-30 ·Pages 555-68

Imbert A, Eelkema R, Jordan S, Feiner H, Cowin P

Abstract

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 NH(2)-terminal 89 amino acids (Delta N 89 beta-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that Delta N 89 beta-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin Delta N 89 beta-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 N89 beta-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, Delta N 89 beta-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.

MeSH Terms
Adenocarcinoma/etiology,genetics Animals Cell Differentiation Cyclin D1/genetics Cytoskeletal Proteins/genetics Cytosol Epithelial Cells Female Male Mammary Glands, Animal/anatomy & histology,cytology,growth & development Mammary Neoplasms, Animal/etiology,genetics Mice Mice, Mutant Strains Mice, Transgenic Pregnancy Proto-Oncogene Proteins c-myc/genetics Reproduction Sequence Deletion Sex Characteristics Sexual Maturation/physiology Tissue Distribution Trans-Activators Up-Regulation beta Catenin
Chemicals
CTNNB1 protein, mouse Cytoskeletal Proteins Proto-Oncogene Proteins c-myc Trans-Activators beta Catenin Cyclin D1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Imbert A
Department of Cell Biology, New York University Medical School, New York, New York 10016, USA.
Eelkema R
Jordan S
Feiner H
Cowin P
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.153.3.555
Published
2001-04-30
Pages
555-68
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2190562
Subset
IM
Grants
NIGMS NIH HHS · GM47429 · United States
External Links
PubMed source DOI: 10.1083/jcb.153.3.555 PMC Full Text View journal details
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