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Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency

Gallagher, Ronald C. J., Hay, Trevor, Meniel, Valerie, Naughton, Catherine, Anderson, Thomas J., Shibata, Hiroyuki, Ito, Masaki, Clevers, Hans, Noda, Tetsuo, Sansom, Owen J., Mason, John O. and Clarke, Alan Richard 2002. Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency. Oncogene 21 (42) , pp. 6446-6457. 10.1038/sj.onc.1205892

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: Apc; Tcf-1; mammary; acanthoma; cre.
Publisher: Nature Publishing
ISSN: 0950-9232
Last Modified: 18 Jan 2018 21:07
URI: http://orca.cf.ac.uk/id/eprint/61372

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