Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen action is regulated at the receptor level by regulation of expression of estrogen receptors, and at the pre-receptor level by interconversions between the active hormone (estradiol) and its inactive counterparts (estrone, estrone-sulfate). In peripheral tissues, estrogens can be produced via the aromatase or the sulfatase pathways. Aromatase converts androstenedione and testosterone to estrone and estradiol, respectively, and sulfatase releases estrogens from inactive sulfates, while sulfotransferase catalyzes the reverse reaction. In both pathways, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are of paramount importance as they catalyze activation of estrone to estradiol and inactivation of estradiol to estrone. These enzymes belong to either the short-chain dehydrogenase/reductase (SDR) or the aldo-keto reductase (AKR) protein superfamilies. Differential expression of these pre-receptor regulatory enzymes can lead to high estradiol concentrations, which have been implicated in the development of different diseases. Here, we have examined gene expression levels of estrogen-metabolizing enzymes, as six SDRs (17beta-HSD types 1, 2, 4, 7, 8, 12) and one AKR (17beta-HSD type 5; AKR1C3), of aromatase, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), and of the alpha and beta estrogen receptors (ERs), in breast cancer (MCF-7), endometrial cancer (Ishikawa), choriocarcinoma (JEG3) and liver cancer (HepG2) cell lines. After RNA isolation and cDNA synthesis, real-time PCR analyses were performed. The expression of AKR1C3 was examined also at the protein level. Our data show that in all four cancer cell lines, estradiol can be synthesized from estrone by the action of 17beta-HSD type 12, or from estrone-sulfate by sulfatase. In JEG3 and HepG2 cells, estradiol can be formed from androgens by aromatase and 17beta-HSD type 1. Also in HepG2 cells, AKR1C3, which converts androstenedione to testosterone, in concert with aromatase might be responsible for estradiol formation. In MCF7 and Ishikawa cells, estradiol exerts its actions through ERalpha, while in JEG3 and HepG2 cells, it may act through non-ER-mediated pathways.
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PMID:Expression of 17beta-hydroxysteroid dehydrogenases and other estrogen-metabolizing enzymes in different cancer cell lines. 1902 35

Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it's effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%). Western blotting and qRT-PCR assay indicated that both in vitro and in vivo Sulf-1 was down-regulated by 75% and 68% and led to up regulation of Msln by 55% in shRNA-transfected-Sulf-1-Hca-P cells compared with Hca-P and nonspecific sequence control plasmid transfected Hca-P cell (shRNA-Nc-Hca-P). The in vitro proliferation, migration and invasion potentials were significantly enhanced following Sulf-1 stable down-regulation. In addition, Sulf-1 knock-down significantly promoted tumor growth and increased LNM rates of shRNA-Sulf-1-Hca-P-transplanted mice by 78.6% (11 out of 14 lymph nodes were positive of cancer). Consistent with our previous work, we confirmed that Sulf-1 plays an important role in hepatocarcinoma cell proliferation, migration, invasion and metastasis. The interaction between Sulf-1 and Msln is a potential therapeutic target in the development of liver cancer therapy.
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PMID:Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin. 2927 59