@entity1412 ( @entity1412 ) inactivating mutations are present in most @entity1 @entity14 . The @entity1412 protein regulates the b-catenin protein pool that functions as a co-activator of T cell factor (TCF)-regulated transcription in Wnt pathway signaling. We studied effects of reduced dosage of the @entity12401 gene encoding b-catenin in Apc-mutation-induced colon and ovarian @entity19 tumorigenesis and cell culture models. Concurrent somatic inactivation of one @entity12401 allele, dramatically inhibited Apc mutation-induced @entity1412 and greatly extended Apc-mutant @entity19 survival. @entity12401 hemizygous dose markedly inhibited increases in b-catenin levels in the cytoplasm and nucleus following Apc inactivation in colon epithelium, with attenuated expression of key b-catenin/TCF-regulated target genes, including those encoding the EphB2/B3 receptors, the stem cell marker @entity42804 , and @entity18122 , leading to maintenance of crypt compartmentalization and restriction of stem and proliferating cells to the crypt base. A critical threshold for b-catenin levels in TCF-regulated transcription was uncovered for Apc mutation-induced effects in colon epithelium, along with evidence of a feed-forward role for b-catenin in @entity12401 gene expression and @entity12401 transcription. The active b-catenin protein pool was highly sensitive to @entity12401 transcript levels in @entity694 cells. In @entity19 @entity43 ( @entity43 ) arising from Apc- and @entity2370 -inactivation, while @entity12401 hemizygous dose affected b-catenin levels and some b-catenin/TCF target genes, @entity18122 induction was retained and @entity43 arose in a fashion akin to that seen with intact @entity12401 gene dose. Our findings indicate @entity12401 gene dose exerts tissue-specific differences in Apc mutation-instigated tumorigenesis. Differential expression of selected b-catenin/TCF-regulated genes, such as @entity18122 , likely underlies context-dependent effects of @entity12401 gene dosage in tumorigenesis.

Tissue-Specific Effects of Reduced b-catenin Expression on XXXX Mutation-Instigated Tumorigenesis in @entity19 Colon and Ovarian Epithelium.

@entity1 :: ('9606', 'Species') :: ['human'] @entity43 :: ('MESH:D010051', 'Disease') :: ['OEAs', 'ovarian endometrioid adenocarcinomas'] @entity18122 :: ('17869(Tax:10090)', 'Gene') :: ['Myc'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity42804 :: ('14160(Tax:10090)', 'Gene') :: ['Lgr5'] @entity2370 :: ('19211(Tax:10090)', 'Gene') :: ['Pten'] @entity12401 :: ('12387(Tax:10090)', 'Gene') :: ['Ctnnb1', 'CTNNB1'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancers and some other cancers'] @entity1412 :: ('MESH:D011125', 'Disease') :: ['Adenomatous polyposis coli', 'colon polyposis', 'APC'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer']
@entity1412 :: (MESH:D011125,Disease) :: ['Adenomatous Polyposis Coli']
