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PubMed · 10508699

APC: the plot thickens.

M Bienz
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Abstract

Adenomatous polyposis coli (APC) is an important tumour suppressor in the human colon. It is conserved between human and flies, and promotes, together with Axin and glycogen synthase kinase 3 (GSK3), the degradation of the Wnt-signalling effector beta-catenin. Recent experiments have shaped our understanding of how Axin and GSK3 function but the role of APC in this process remains elusive.

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Adenomatous Polyposis ColiAdenomatous Polyposis Coli ProteinAnimalsCalcium-Calmodulin-Dependent Protein KinasesCytoskeletal ProteinsDrosophilaGlycogen Synthase Kinase 3Glycogen Synthase KinasesHumansHydrolysisPhosphorylationTrans-Activatorsbeta CateninJournal ArticleReview

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M Bienz. 1999. APC: the plot thickens.. https://doi.org/10.1016/s0959-437x(99)00016-7

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PubMed2000

Chemopreventative activity of crude hydroxymatairesinol (HMR) extract in Apc(Min) mice [corrected].

We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)(Min) mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26.6+/-11.0, P<0.05) in mice fed the TNS tumor promoter insulin and HMR when compared with the insulin and insulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-catenin level in adenoma tissue was significantly elevated (P=0.008-0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, beta-catenin in the insulin (3.15+/-2.9 relative units) and insulin/rye (5.17+/-6.94 relative units) groups was also significantly higher (P=0.003-0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5+/-0.5 and 0.35+/-0.39 relative units). However, HMR was able to restore nuclear beta-catenin level of the adenoma tissue (0.41+/-0.25 relative units) to the level found in the surrounding mucosa (0.36+/-0.28 relative units).

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