Thirty-nine CTNNB1 mutated EECs and 40 CTNNB1 wild-type EECs were identified from a cohort of previously sequenced endometrial carcinomas using a targeted next-generation sequencing panel.
<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.
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.
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.
We observed that SOX17 expression levels were relatively high in stage I EC specimens, and were significantly correlated with the epithelial cadherin (E-cadherin) and β-catenin expression.
Nuclear expression of β-catenin is an accurate immunohistochemical surrogate of CTNNB1 exon 3 mutations and thus might be considered in the risk stratification of endometrial cancer.
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.
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.
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.
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.
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.
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).
To evaluate the expression of four genetic markers (PTEN, BCL2, MLH1, and CTNNB1), linked to endometrial carcinogenesis, in endometrial polyps of patients with and without postmenopausal bleeding in order to determine whether symptomatic endometrial polyps have a genetic phenotype similar to that of endometrial cancer.
The reduced expression of β-catenin and E-cadherin is associated with the tumoral epithelial-mesenchymal transition process, a key event in the development of endometrial carcinoma.
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.
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.
We studied the expression of phosphorylated mammalian target of rapamycin, PTEN, and β-catenin and their relationship with clinicopathologic features, molecular factors (microsatellite instability, mismatch repair, and BRAF genes) and patients' survival in a series of 260 nonconsecutive endometrial carcinomas.
Western blotting, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to evaluate the expression of Wnt10b and some key proteins of the Wnt/β-catenin pathway, proliferation and apoptosis in EC.
These data suggest Sox7 is a negative regulator of Wnt/β-catenin signaling pathway through impeding the transcriptional machinery of β-catenin/TCF/LEF-1 transcriptional complex, and the loss of expression may be involved in the pathogenesis of endometrial cancer.