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)

Acteoside and martynoside are plant phenylpropanoid glycosides exhibiting anticancer, cytotoxic and antimetastatic activities. We investigated their potential to activate estrogen receptor isoforms ERalpha and ERbeta in HeLa cells transfected with an estrogen response element (ERE)-driven luciferase (Luc) reporter gene and an ERalpha or ERbeta expression vector. Their estrogenic/antiestrogenic effects were also assessed in breast cancer cells (MCF7), endometrial cancer cells (Ishikawa) and osteoblasts (KS483), by measuring IGFBP3 levels, cell viability and number of mineralized nodules, respectively, seeking for a natural selective estrogen receptor modulator (SERM). Acteoside and martynoside antagonized both ERalpha and ERbeta (p<0.001), whereas they reversed the effect of E(2) mainly via ERalpha (p<0.001). Martynoside was a potent antiestrogen in MCF-7 cells, increasing, like ICI182780, IGFBP3 levels via the ER-pathway. In osteoblasts, martynoside induced nodule mineralization, which was abolished by ICI182780, implicating an ER-mediated mechanism. Furthermore, its antiproliferative effect on endometrial cells suggests that martynoside may be an important natural SERM. Acteoside was an antiestrogen in breast cancer cells and osteoblasts, without any effect on endometrial cells. Our study suggests that the nature is rich in selective ERalpha and ERbeta ligands, the discovery of which may lead to the development of novel neutraceutical agents.
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PMID:Acteoside and martynoside exhibit estrogenic/antiestrogenic properties. 1619 57

Endometrial cancer is the most common gynecological malignancy, with more than 280,000 cases occurring annually worldwide. Although previous studies have identified important common somatic mutations in endometrial cancer, they have primarily focused on a small set of known cancer genes and have thus provided a limited view of the molecular basis underlying this disease. Here we have developed an integrated systems-biology approach to identifying novel cancer genes contributing to endometrial tumorigenesis. We first performed whole-exome sequencing on 13 endometrial cancers and matched normal samples, systematically identifying somatic alterations with high precision and sensitivity. We then combined bioinformatics prioritization with high-throughput screening (including both shRNA-mediated knockdown and expression of wild-type and mutant constructs) in a highly sensitive cell viability assay. Our results revealed 12 potential driver cancer genes including 10 tumor-suppressor candidates (ARID1A, INHBA, KMO, TTLL5, GRM8, IGFBP3, AKTIP, PHKA2, TRPS1, and WNT11) and two oncogene candidates (ERBB3 and RPS6KC1). The results in the "sensor" cell line were recapitulated by siRNA-mediated knockdown in endometrial cancer cell lines. Focusing on ARID1A, we integrated mutation profiles with functional proteomics in 222 endometrial cancer samples, demonstrating that ARID1A mutations frequently co-occur with mutations in the phosphatidylinositol 3-kinase (PI3K) pathway and are associated with PI3K pathway activation. siRNA knockdown in endometrial cancer cell lines increased AKT phosphorylation supporting ARID1A as a novel regulator of PI3K pathway activity. Our study presents the first unbiased view of somatic coding mutations in endometrial cancer and provides functional evidence for diverse driver genes and mutations in this disease.
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PMID:Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. 2302 88

The aim of the current study was to investigate the underlying mechanism of S-phase kinase associated protein 2 (Skp2) gene inhibition by lentivirus-mediated RNA interference (RNAi) on the cell cycle, apoptosis and proliferation of endometrial carcinoma HEC-1-A cells. A lentivirus shRNA vector targeting Skp2 was constructed and transfected into HEC-1-A cells. HEC-1-A cells transfected with a scramble sequence were used as negative controls. The mRNA and protein expression of Skp2, p27, cyclin D1 and caspase-3 were detected via reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The effects of Skp2 inhibition on the cell cycle, apoptosis and proliferation of HEC-1-A cells were detected using flow cytometry and a cell counting kit-8. Skp2 co-expression data was analyzed using Oncomine and TCGA databases. The positive recombinant viral clones were identified via PCR and confirmed via sequencing. The mRNA and protein expression of Skp2 were significantly decreased in HEC-1-A cells transfected with the lentiviral vectors compared with the negative control. In addition, there were no significant changes in the mRNA expression of p27 and cyclin D1; however, the protein levels of p27 and cyclin D1 were upregulated and downregulated, respectively, in HEC-1-A cells transfected with lentiviral vectors compared with negative controls. RNAi-induced Skp2 inhibition exerted an anti-proliferative effect by inducing cell cycle arrest, however cell apoptosis was not significantly affected. In the TCGA database, Skp2 expression positively associated with IGF2R, IGF2BP3, IGFBP1 and CCNF, while Skp2 expression negatively associated with IGF2, IGFBP6, IGFBP7 and IGFBP3. RNAi-induced Skp2 inhibition upregulated the protein expression of p27 and downregulated the protein expression of cyclin D1. The expression of Skp2 in endometrial cancer may therefore be regulated by the insulin-like growth factor 1 receptor signaling pathway.
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PMID:Effects of RNAi-induced Skp2 inhibition on cell cycle, apoptosis and proliferation of endometrial carcinoma cells. 3098 23