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)

An increased risk of developing endometrial cancer is observed in breast cancer patients treated with tamoxifen (TAM) and in healthy women undergoing TAM chemoprevention therapy. TAM-DNA adducts were detected in the endometrium of women taking TAM (Shibutani, S., et al. (2000) Carcinogenesis 21, 1461-1467) and are formed primarily through O-sulfonation of alpha-hydroxytamoxifen (alpha-OHTAM). To explore the genotoxicic mechanisms of TAM, TAM was incubated with one of multiple human cytochrome P450 enzymes, i.e., P450 1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3A, or 4F3B, in a NADPH regenerating system, and the metabolites were identified using HPLC/UV analysis with authentic standards. Among the 18 human P450 enzymes, P450 3A4 generated a significant amount of alpha-OHTAM. When some rat P450 enzymes were examined, P450 3A2 also catalyzed alpha-hydroxylation of TAM. Similarly, human P450 3A4 and rat P450 3A1 and 3A2 converted toremifene (TOR, a chlorinated TAM analogue) to alpha-hydroxytoremifene (alpha-OHTOR). The formation of alpha-OHTAM and alpha-OHTOR by these P450 enzymes was confirmed by tandem mass spectroscopy. Only the P450 3A subfamily enzymes are able to alpha-hydroxylate TAM and TOR. Although the formation of alpha-OHTOR by these enzymes was much higher than that of alpha-OHTAM, TOR is known to be much less genotoxic than TAM. The results support our proposed mechanism that the lower genotoxicity of TOR is due to limited O-sulfonation of alpha-OHTOR by hydroxysteroid sulfotransferases, resulting in the poor formation of DNA adducts (Shibutani, S., et al. (2001) Cancer Res. 61, 3925-3931).
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PMID:Alpha-hydroxylation of tamoxifen and toremifene by human and rat cytochrome P450 3A subfamily enzymes. 1297 2

Long noncoding RNAs (lncRNAs) are RNA molecules more than 200 nucleotides in length that do not encode proteins. Recent studies have reported increasing numbers of functional lncRNAs. Maternally expressed gene 3 (MEG3) is a maternally imprinted gene encoding an lncRNA that plays a tumor suppressor role in various tumors. However, there has been rare report on mechanism of tumorigenesis and progression of endometrial carcinoma. In the present study, we found significantly lower MEG3 expression in endometrial carcinoma tissues than in normal endometrial tissues. MEG3 overexpression inhibited endometrial cancer cell proliferation, invasion, and metastasis; promoted apoptosis; and inhibited the activation of the phosphoinositide 3-kinase (PI3K)/m-TOR signaling pathway. RNA immunoprecipitation assay (RIP) showed that MEG3 can combine directly with PI3K. Tumor xenograft implantation in nude mice showed that MEG3 could significantly suppress tumor growth. These findings provide potential new therapeutic targets for treating endometrial cancer.
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PMID:LncRNA MEG3 inhibit endometrial carcinoma tumorigenesis and progression through PI3K pathway. 2909 70