Mutations in Apc and p53 synergize to promote mammary neoplasia

Meniel, V., Hay, T., Douglas-Jones, A., Sansom, O. and Clarke, A. (2005) Mutations in Apc and p53 synergize to promote mammary neoplasia. Cancer Research, 65(2), pp. 410-416.

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Mutations of Apc and p53 have both been implicated in human and murine mammary neoplasia. To investigate potential interactions between Apc and. p53, we conditionally inactivated Ape in both the presence and the absence oil functional p53. Ape deficiency on its own leads to the development of metaplasia but not neoplasia. We. show here that these areas of metaplasia are characterized by elevated levels of both p53 and p21. In the additional absence of p53, there is rapid progression to neoplasia, with 44.4% of lymphoma-free mice developing a mammary tumor with earliest observed onset at pregnancy. To investigate the mechanism by which p53 deficiency accelerates neoplasia, we used the Rosa26R reporter strain as a marker of Cre-mediated recombination and show a role for p53 in the loss of Apc-deficient cells. This role seems limited to pregnancy and subsequent time points. We therefore show clear synergy between these two mutations in mammary gland neoplasia and present data to suggest that at least one mechanism for this acceleration is the p53-dependent loss of Apc-deficient cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Sansom, Professor Owen
Authors: Meniel, V., Hay, T., Douglas-Jones, A., Sansom, O., and Clarke, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Research

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