B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver

Reed, Karen Ruth ORCID: https://orcid.org/0000-0002-7467-1718, Athineos, Dimitris, Meniel, Valerie, Wilkins, Julie Ann, Ridgeway, Rachel A., Burke, Zoe D., Muncan, Vanesa, Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X and Sansom, Owen J. ORCID: https://orcid.org/0000-0001-9540-3010 2008. B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proceedings of the National Academy of Sciences of the United States of America 105 (48) , pp. 18919-18923. 10.1073/pnas.0805778105

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Abstract

Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Wnt signaling is key. Here, using cre-lox technology, we deleted the Apc gene in the adult mouse liver and observed a rapid increase in nuclear β-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors β-catenin and c-Myc. β-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Wnt pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Wnt targets being β-catenin-dependent but c-Myc-independent in the liver.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	c-Myc; Wnt signaling
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Last Modified:	06 Jan 2023 02:07
URI:	https://orca.cardiff.ac.uk/id/eprint/8771

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