Cyclin D1 is not an immediate target of β-Catenin following Apc loss in the intestine

Sansom, Owen J., Reed, Karen Ruth ORCID: https://orcid.org/0000-0002-7467-1718, van de Wetering, M., Muncan, V., Winton, D. J., Clevers, H. and Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X 2005. Cyclin D1 is not an immediate target of β-Catenin following Apc loss in the intestine. Journal of Biological Chemistry 280 (31) , pp. 28463-28467. 10.1074/jbc.M500191200

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Abstract

Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1 immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1-/- background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions developing 20 days after Apc loss. In these circumstances, all adenomas (but not smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we analyzed whether cyclin D1 deficiency affected adenoma formation 20 days following induced loss of Apc. Unlike AhCre+ Apcfl/fl mice (which all developed adenomas), doubly mutant AhCre+ Apcfl/fl cyclin D1-/- mice only developed small lesions. Taken together, this argues that cyclin D1 up-regulation in intestinal neoplasia is important for tumor progression rather than initiation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	25 Oct 2022 10:11
URI:	https://orca.cardiff.ac.uk/id/eprint/61351

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