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)

Estrogen sulfoconjugation previously was reported in normal endometrium and in RL95-2 cells, a cell line derived from a human endometrial cancer maintained in continuous in vitro culture. In the present study the estrogen sulfurylation activity in the cytosolic fraction of RL95-2 cells was characterized using [3H]estrone as substrate. Estrone sulfate was separated from unreacted estrone by thin layer chromatography. Activity was proportional to cytosol concentration, with a pH optimum at pH 8. There was marked temperature dependence between 24 and 40 C. The apparent Km for estrone conjugation was 3.6 nM, with a maximum velocity of 135 fmol/micrograms DNA . h. No complex kinetic behavior was found at estrone concentrations up to 1 microM. The apparent Km for the cosubstrate 3'-phosphoadenosine 5'-phosphosulfate was 0.6 microM. Inhibition experiments demonstrated that the sulfurylating activity studied under these conditions was specific for estrogens. Only estradiol and estriol, in addition to estrone itself, inhibited conjugation to any significant degree. Dehydroepiandrosterone had only 1% the inhibitory activity of estrone. Other androgens, corticoids, progestins, phenols, nonsteroidal estrogens and antiestrogens, and bile acids had no significant effects on the sulfurylation of estrone. An estrogen-sulfoconjugating activity with the characteristics of estrogen sulfotransferase (EST) was demonstrated in RL95-2 cells. The Km of EST for estrone in the RL95-2 cells closely approximated the value reported for the enzyme in normal endometrium. The affinity of EST for estrogens is within the range of the Kd of estrogen receptor and of the physiological concentrations of estrogens reported in the endometrium, suggesting that EST could serve as a regulator of intracellular estrogen levels.
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PMID:Characterization of cytosolic estrogen sulfotransferase from RL95-2 endometrial cancer cells. 659 68

Understanding the factors which alter estrogen metabolism and activity in endometrial tissue is important because unopposed estrogen stimulation is an important risk factor in the development of endometrial carcinoma. The cyclic progression of the endometrium through proliferative and secretory phases is normally under the control of the ovarian hormones beta-estradiol (E2) and progesterone. One mechanism by which progesterone inhibits the activity of E2 in secretory endometrium is by elevating the degree of E2 sulfation, thereby reducing its ability to bind to the estrogen receptor and elicit a cellular response. Our laboratories have investigated the cytosolic sulfotransferases (STs) found in biopsies of both proliferative and secretory endometrium obtained from five normal pre-menopausal women who were not taking any drugs or steroids. Two of the human cytosolic STs were detected in human endometrial tissues. The phenol-sulfating form of phenol ST (P-PST) was found at varying levels in cytosol from both proliferative and secretory endometrium in all of the women studied but with no consistent correlation to the phase of the menstrual cycle. In contrast, estrogen ST (EST) was not detected in the proliferative endometrial cytosol of any of the women studied but was consistently found in all of the secretory endometrial cytosols. The presence and levels of these STs was confirmed by ST activity studies, immunoblot analysis and Northern blot analysis. These results indicate that the expression of EST in human endometrial tissues varies with the phase of the menstrual cycle and is most likely regulated by progesterone secreted from the ovaries.
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PMID:Identification and characterization of cytosolic sulfotransferases in normal human endometrium. 956 56

Levels and activity of the enzyme estrogen sulfotransferase (EST) have been reported to play an important role in the regulation of in situ estrogen levels in human breast, prostate, and endometrial cancer. To better understand growth progression in endometrial stromal sarcomas (ESS), estrogen-dependent tumors, we analyzed the expression of EST in a series of 29 ESS. Archival formalin-fixed, paraffin-embedded material was analyzed immunohistochemically with a monoclonal antibody to EST using the peroxidase-antiperoxidase method. A score was calculated based on the percentage of positive tumor cells and staining intensity. EST staining was identified in 5 of 29 (18%) ESS and was scored as weakly positive, while 24 of 29 (82%) ESS were negative for EST. We demonstrate that a subset of ESS express EST, which may allow them to inactivate intratumoral estrogens. ESS without EST expression may have increased levels of biologically active estrogen, which explains the tumor progression of this entity and these patients may be at increased risk for recurrences and metastases.
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PMID:Estrogen sulfotransferase expression in endometrial stromal sarcomas: an immunohistochemical study. 1719 18