<b>Methods:</b> Lentiviral particles carrying human HDGF short hairpin RNA (shHDGF-1, -2, and -3) vector and plasmids for HDGF, DDX5, and β-catenin expression were, respectively introduced into EC cells to evaluate the effects and molecular mechanisms underlying EC cell proliferation, migration, invasion, and metastasis.
A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and beta-catenin.
Accumulation of mutant beta-catenin could contribute to the development of a subset of endometrial carcinomas, particularly those of the early-onset type.
Analysis of human endometrial biopsy samples and available databases reveals significant and positive correlations of MRP4 with β-catenin and Wnt/β-catenin target genes in the receptive endometrium in IVF, ectopic endometriotic lesions and endometrial cancers.
Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors.
Ectopic overexpression of Gli1 into endometrial cancer cells led to reduced expression of beta-catenin in cell cytoplasm and increased expression of beta-catenin in the nuclei.
Forty-nine ECs (three tumour blocks/case) were selected with alterations in POLE (n=10), CTNNB1 (n=8), p53 (n=10), mismatch repair (n=11), L1CAM (n=10), and ECs without any of these markers (n=9).
Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling.Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.
Further experiments indicated miR-652 overexpression can activate the Wnt/β-catenin pathway and RORA can downregulate β-catenin and function as a tumor suppressor in endometrial cancer.
Furthermore, patient samples (hormone-treated endometria, hyperplasia, and endometrial cancer) were stained for Wnt activation using nuclear beta-catenin and CD44.
Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing.
In accordance with studies on sporadic cancers, abnormal accumulation of beta-catenin protein in nuclei occurred much less frequently in HNPCC-related ECs than CRCs, which may reflect organ-specific differences in their pathogenesis.
In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors.
In this study, we have examined immunoreactivity for the cell cycle regulatory proteins cyclin D1, p16 and beta-catenin in 22 endometrial carcinomas, specifically comparing the results in conventional tumor areas and in foci in which the glands exhibited microcystic, elongated and fragmented appearances.
More specifically, the aberrant expression of major EMT markers, such as lower expressions of E-cadherin and alpha-catenin, and overexpressions of N-cadherin, beta-catenin, vimentin, and matrix metalloproteinases, have been reported in ovarian, cervical, and endometrial cancers.
Moreover, a reduction in CaSR expression in endometrial cancer relative to normal specimens was evident by immunohistochemistry and was positively associated with E-cadherin, but not β-catenin, expression.
MTT assay is performed to determine the growth inhibition ratio of the DNA methyltransferase inhibitor 5-AZA for endometrial carcinoma cells, and the real-time fluorescence quantification PCR (qRT-PCR) was used to detect the mRNA expression of SOX17, β-catenin, and CyclinD1 in endometrial carcinoma tissues before and after using 5-AZA to treat the endometrial carcinoma cell line.
Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs.