Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.
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.
Imbert
A
A
Department of Cell Biology, New York University Medical School, New York, New York 10016, USA.
Eelkema
R
R
Jordan
S
S
Feiner
H
H
Cowin
P
P
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D019938:Cyclin D1 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003600:Cytosol; D004847:Epithelial Cells; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development*; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012098:Reproduction; D017384:Sequence Deletion; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000502:physiology; D014018:Tissue Distribution; D015534:Trans-Activators; D015854:Up-Regulation; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1