Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency.
Apc (adenomatous polyposis coli) encodes a tumour suppressor gene that is mutated in the majority of colorectal cancers. Recent evidence has also implicated Apc mutations in the aetiology of breast tumours. Apc is a component of the canonical Wnt signal transduction pathway, of which one target is Tcf-1. In the mouse, mutations of both Apc and Tcf-1 have been implicated in mammary tumorigenesis. We have conditionally inactivated Apc in both the presence and absence of Tcf-1 to examine the function of these genes in both normal and neoplastic development. Mice harbouring mammary-specific mutations in Apc show markedly delayed development of the mammary ductal network. During lactation, the mice develop multiple metaplastic growths which, surprisingly, do not spontaneously progress to neoplasia up to a year following their induction. However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma.
Gallagher
Ronald C J
RC
Department of Biomedical Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
Hay
Trevor
T
Meniel
Valerie
V
Naughton
Catherine
C
Anderson
Thomas J
TJ
Shibata
Hiroyuki
H
Ito
Masaki
M
Clevers
Hans
H
Noda
Tetsuo
T
Sansom
Owen J
OJ
Mason
John O
JO
Clarke
Alan R
AR
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D001940:Breast / Q000254:growth & development*; D018267:Carcinoma, Acinar Cell / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D016259:Genes, myc / Q000502:physiology; D005838:Genotype; D018095:Germ-Line Mutation; D051538:Hepatocyte Nuclear Factor 1-alpha; D007124:Immunoenzyme Techniques; D019426:Integrases; D007763:Lac Operon / Q000502:physiology; D051821:Lymphoid Enhancer-Binding Factor 1; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008679:Metaplasia / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012878:Skin Neoplasms / Q000473:pathology*; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency*; D014764:Viral Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D051176:beta Catenin; D019938:Cyclin D1; C045073:Cre recombinase; D019426:Integrases