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.
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Acknowledgements
This work was supported by the Royal Society, the BBSRC and the Association for International Cancer Research (AICR). We are grateful to Inke Nathke for the gift of the anti-APC antibody.
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Gallagher, R., Hay, T., Meniel, V. et al. Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency. Oncogene 21, 6446–6457 (2002). https://doi.org/10.1038/sj.onc.1205892
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DOI: https://doi.org/10.1038/sj.onc.1205892
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