Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analysed p16 gene alteration and p16, cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D1, cyclin D2, cyclin D3 and retinoblastoma protein (pRb) expression in ten normal endometriums (PE), 18 endometrial hyperplasias (EH) and 35 endometrial cancers (EC). Two of ten PE (20%), nine of 18 EH (50.0%) and 29 of 35 EC (82.9%) exhibited p16 nuclear staining. p16 expression was significantly higher in EC than EH (P = 0.0119). In the six p16 (-) EC, one was considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene and three had methylation in 5'CpG island in the promoter region of the p16 gene, whereas none showed such reduced gene dosage and four had methylation in the nine p16 (-) EH. Strong CDK4 staining was observed in 12 of 35 EC (34.3%) and one of 18 EH (5.6%). The strong expression of CDK4 was higher in EC than in EH (P = 0.0399). The expression of CDK4 was higher in EH than PE (P = 0.0054). The abnormalities of p16-cyclin D/CDK-pRb pathway were detected in 18 of 35 EC (51.4%). In conclusion, the expression of p16 and CDK4 may be an early event in the neoplastic transformation of endometrial cancer.
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PMID:The role of p16-cyclin d/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma. 1068 82

MicroRNAs (miRNAs) play an important role in the development and progression of endometrial carcinoma (EC). Recently, several studies have shown that microRNA-124 (miR-124) is downregulated in various cancers, which can affect tumor initiation and maintenance. However, the effects of miR-124 on EC are largely unknown. In this study, we identified the under-expression of miR-124 in 35 paired EC tissues and adjacent normal tissues. Further, functional experiments found that ectopic expression of miR-124 markedly suppressed cell proliferation, migration, and invasion of EC cells. It also induced cell apoptosis and G1-phase cell cycle arrest. Moreover, we identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124, and over expression of miR-124 not only induced changes in STAT3 expression but also altered expression of its target genes, cyclin D2 and matrix metalloproteinase 2, in the human endometrial carcinoma cell line HEC-1B. In addition to targeting STAT3 directly, we found that miR-124 suppresses phosphorylation of STAT3 through targeting IL-6R indirectly. Restored STAT3 expression through treatment with IL-6 cytokine partly abolished miR-124-mediated cell cycle arrest and apoptosis induction. These results combined with the tumorigenetic role of STAT3 in HEC-1B cells suggest that the antitumor effects of miR-124 are achieved, at least partly, through down regulation of STAT3 mRNA and its downstream target genes. Therefore, inhibition of constitutively activated STAT3 by ectopic expression of miR-124 in EC may provide a novel therapeutic strategy for the treatment of EC.
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PMID:miR-124 functions as a tumor suppressor in the endometrial carcinoma cell line HEC-1B partly by suppressing STAT3. 2428 65

Our previous study showed that progesterone (P4) can specifically regulate the expression of some microRNAs (miRNAs) in endometrial epithelium. In the present study, we verified the P4-dependent expression of miR-145/miR-143 in endometrial epithelial cells, explored the regulative mechanism of the P4 receptor (PR), and investigated their effects on the proliferation of endometrial epithelial cells. Our results showed that P4 can induce the expression of miR-145/143 in endometrial epithelial cells by acting on the PR A subtype. P4-induced miR-145/143 can inhibit the expression of cyclin D2 by binding to cyclin D2 mRNA 3'UTR. It can also inhibit cell proliferation in mouse endometrial epithelium by arresting the cell cycle during the G1-S checkpoint. Furthermore, miR-145 and miR-143 can inhibit the proliferation of human endometrial cancer cells. In conclusion, P4-induced miR-145/miR-143 is an important regulator in the proliferation of endometrial epithelial cells, and it can also inhibit the proliferation of human endometrial cancer cells. Our study indicates miRNAs are important mechanism of P4 in inhibiting the proliferation of endometrial epithelial cells. And these miRNAs are potential candidates for the diagnosis of endometrial cancer and therapeutic targets.
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PMID:Progesterone-Induced miR-145/miR-143 Inhibits the Proliferation of Endometrial Epithelial Cells. 2966 Nov