Beta-catenin and Tcfs in mammary development and cancer.
Beta-catenin regulates cell-cell adhesion and transduces signals from many pathways to regulate the transcriptional activities of Tcf/Lef DNA binding factors. Gene ablation and transgenic expression studies strongly support the concept that beta-catenin together with Lef/Tcf factors act as a switch to determine cell fate and promote cell survival and proliferation at several stages during mammary gland development. Mice expressing the negative regulator of Wnt/beta-catenin signaling (K14-Dkk) fail to form mammary buds, and those lacking Lef-1 show an early arrest in this process at stage E13.5. Stabilized deltaN89beta-catenin initiates precocious alveologenesis during pubertal development, and negative regulators of endogenous beta-catenin signaling suppress normal alveologenesis during pregnancy. Stabilized beta-catenin induces hyperplasia and mammary tumors in mice. Each of the beta-catenin-induced phenotypes is accompanied by upregulation of the target genes cyclin D1 and c-myc. Cyclin D1, however, is dispensable for tumor formation and the initiation of alveologenesis but is essential for later alveolar expansion.
Hatsell
Sarah
S
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Rowlands
Tracey
T
Hiremath
Minoti
M
Cowin
Pamela
P
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002470:Cell Survival; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D008321:Mammary Glands, Animal / Q000196:embryology; D042361:Mammary Glands, Human / Q000196:embryology; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018396:Mucin-1 / Q000378:metabolism; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D018396:Mucin-1; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D019938:Cyclin D1