Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]-Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.
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PMID:Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens. 237

Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells. It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17 beta-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormone-dependent mammary cancer.
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PMID:Importance of estrogen sulfates in breast cancer. 256 May 11

The activity of the two membrane-bound sulfatases, estrone and dehydroepiandrosterone sulfatases, are reported in human breast carcinoma tissues. In 21 tested tumors (12 from post-menopausal women and 9 from nonmenopausal women), the two sulfatases were consistently present. The apparent Km values for estrone and dehydroepiandrosterone sulfatases were, respectively, 6.8 and 14.9 microM. In terms of maximal velocity, the sulfatase activities are not correlated to the estrogen or progesterone receptor status of the tumors or to the hormonal status of the donors. It may be concluded that these two activities are not hormone dependent. Estrone sulfate, the substrate of estrone sulfatase, has been measured in plasma of postmenopausal women. The mean levels (nmol/liter) of plasma estrone sulfate were compared in post-menopausal women with (n = 51) or without (n = 39) breast cancer. For the first age group (48 to 55 years old), no statistically significant difference in these levels was observed [1.91 +/- 1.06 versus 1.50 +/- 1.04 (mean +/- t0.95 (Formula: see text) S.E.)]. For the two other age groups (56 to 65 and 66 to 80 years of age), the differences were statistically significant [1.46 +/- 0.43 versus 0.77 +/- 0.21 (p less than 0.02) and 1.77 +/- 0.53 versus 0.81 +/- 0.22 (p less than 0.01)]. The usefulness of plasma estrone 3-sulfate levels as an indicator of the real estrogen status of postmenopausal women is discussed.
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PMID:Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. 658 63

Estrone and estradiol concentrations in breast tumor tissue are an order of magnitude higher than circulating plasma levels in postmenopausal women with breast cancer. Local production of estrogen in the neoplastic tissue is one of several possible explanations for this plasma/tissue gradient. This study evaluated breast tumor estrogen production via the estrone sulfate to estrone (sulfatase) pathway and compared this with the androstenedione to estrone (aromatase) system in human and rodent mammary tumors. Estrogen production from estrone sulfate was related linearly with time and tissue concentrations, exhibited an apparent Km of 20 microM, and produced a linear Eadie-Hofstee kinetic plot consistent with a single class of enzymatic sites. Measurement of sulfatase in 35 human breast tumors using enzyme saturating conditions revealed estrone production ranging from 0.8-125 mumol/g protein . h. The corresponding range in host mammary tumors was 3.5-7.1 mumol/g protein . h. In human breast tumors, sulfatase activity did not correlate with the levels of estrogen receptor or progesterone receptor. Comparison of sulfatase with aromatase activity in human tumors at physiological levels of substrate revealed estrone formation via sulfatase of 2.8 pmol estrone produced/g protein . h, while aromatase produced only 0.27 pmol/g protein . h. In rat mammary tumors, sulfatase activity was similar to that in human tumors, whereas aromatase activity could not be detected, even with a highly sensitive assay. Thus, estrone sulfatase appears to be the enzyme primarily responsible for intratissue estrone production in hormone-dependent breast carcinomas.
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PMID:In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. 672 22

Estradiol levels in breast tumors from post-menopausal women are similar to those in pre-menopausal women even though plasma estrogens are much lower after the menopause. In situ estrogen production by the tumor provides a potential means of maintaining high estradiol levels in post-menopausal breast cancer tissue. The estrone sulfatase pathway has been proposed as the mediator of in situ estrogen production. A number of studies suggest that estrone sulfate may be converted into estradiol in breast tumors via the catalytic activity of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase. However, these studies used pharmacologic levels of estrogen sulfates and have not shown that physiologic levels can support biologic effects. Accordingly, the present study examined the dose relationship of estrone sulfate to a variety of biologic endpoints in MCF-7 breast cancer cells in culture. These cells converted physiologic concentrations of estrone sulfate to quantities of free estradiol capable of stimulating cell growth. Under these conditions, the nuclear steroids observed were free estrone and estradiol. Increase in cell number after 6 days of exposure to steroid required 100 nM estrone sulfate. However, S-phase, a more sensitive measure of cell proliferation, was stimulated by 0.1 nM estrone sulfate, a clearly physiologic concentration. Stimulation of estrogen-dependent protein markers such as pS2 and progesterone receptor required much higher concentrations of estrone sulfate. These effects were mediated through the estrogen receptor since the pure anti-estrogen, ICI 164384, blocked all effects produced by estrone sulfate. While it has been suggested that anti-estrogens may partly exert their effects by inhibition of sulfatase and 17 beta-hydroxysteroid dehydrogenase, this did not occur under our experimental conditions. These data provide evidence of the relevance of the estrone sulfatase pathway since biologic effects can be demonstrated in response to physiologic concentrations of estrone sulfate.
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PMID:Estrone sulfate promotes human breast cancer cell replication and nuclear uptake of estradiol in MCF-7 cell cultures. 847 38

In the last years there has been an extraordinary development in the synthesis of new progestins. These compounds are classified, in agreement with their structure, in various groups which include progesterone, retroprogesterones, 17alpha-hydroxyprogesterones, 19-norprogesterones, 17alpha-hydroxyprogesterone derivatives, androstane and estrane derivatives. The action of progestins is a function of many factors: its structure, affinity to the progesterone receptor or to other steroid receptors, the target tissue considered, the biological response, the experimental conditions, dose, and metabolic transformation. The information on the action of progestins in breast cancer patients is very limited. Positive response with the progestins: medroxyprogesterone acetate and megestrol acetate was obtained in post-menopausal patients with advanced breast cancer. However, extensive information on the effect of progestins was obtained in in vitro studies using hormone-dependent and hormone-independent human mammary cancer cell lines. It was demonstrated that in the hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, tibolone, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of mRNA of this enzyme. In another series of studies it was also demonstrated that various progestins are very active in inhibiting the 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone or medrogestone stimulate the sulfotransferase for the formation of estrogen sulfates. Consequently, the blockage in the formation of estradiol via sulfatase, or the stimulatory effect on sulfotransferase activity, by progestins can open interesting and new possibilities in clinical applications in breast cancer.
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PMID:Progestins and breast cancer. 969 77

Many human breast tumors are driven by high intratumor concentrations of 17beta-estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequately assessed and remains unclear. To evaluate the role of STS further, we transduced estrogen-dependent MCF-7 human breast cancer cells with a retroviral vector directing the constitutive expression of the human STS gene. Gene integration was confirmed by Southern hybridization, production of the appropriately sized messenger RNA by Northern hybridization, and expression of functional protein by metabolism of [(3)H]estrone sulfate to [(3)H]estrone. Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg protein.h in STS-transduced cells (STS Clone 20), levels comparable to those seen in some human breast tumors. Lower levels of endogenous activity are seen in MCF-7 cells (13.0 pmol estrone/mg protein.h) and in cells transduced with vector lacking the STS gene (Vector 3 cells; 12.0 pmol estrone/mg protein.h). 17beta-Estradiol sulfate induces expression of the progesterone receptor messenger RNA only in STS Clone 20 cells, whereas estrone sulfate produces the greatest stimulation of anchorage-independent growth in these cells. STS Clone 20 cells retain responsiveness to antiestrogens, which block the ability of estrogen sulfate to increase the proportion of cells in both the S and G(2)/M phases of the cell cycle. Consistent with these in vitro observations, only STS Clone 20 cells exhibit a significant increase in the proportion of proliferating tumors in nude ovariectomized mice supplemented with 17beta-estradiol sulfate. The primary activity in vivo appears to be from intratumor STS, rather than hepatic STS. Surprisingly, 17beta-estradiol sulfate appears more effective than 17beta-estradiol when both are administered at comparable concentrations. This effect, which is seen only in STS Clone 20 cells, may reflect differences in the cellular pharmacology of exogenous estrogens compared with those released by the activity of intracellular STS. These studies directly demonstrate that intratumor STS activity can support estrogen-dependent tumorigenicity in an experimental model and may contribute to the promotion of human breast tumors.
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PMID:Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo. 1125 Sep 30

The action of progestins is derived from many factors: structure, affinity for the progesterone receptor or for other steroid receptors, the target tissue considered, the biological response, the experimental conditions, the dose and metabolic transformation. The proliferative response to progestins in human breast cancer cells is contradictory: some progestins inhibit, others stimulate, have no effect at all, or have a dual action. For instance, medroxyprogesterone acetate has a stimulatory effect on breast cancer cells after a short period of treatment, but this effect becomes inhibitory when treatment is prolonged. It has been demonstrated that, in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of the mRNA expression of this enzyme. In another series of studies it was also demonstrated that some progestins are very active in inhibiting 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone and medrogestone stimulate sulfotransferase for the formation of estrogen sulfates. Consequently, the action of progestins in blocking estradiol formation via sulfatase, or in stimulating the effect on sulfotransferase activity, can open interesting and new possibilities in clinical applications in breast cancer.
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PMID:Biological effects of progestins in breast cancer. 1222 86

Developments in the synthesis of different progestins have opened up new possibilities for the biological effects and therapeutic uses of these compounds. The actions of progestins are a function of their structure, affinity to the progesterone receptor or to other steroid receptors, the target tissue considered, the biological response, the experimental conditions, dose, and metabolic transformation. Data on the action of progestins in breast cancer patients are very limited. A positive response with the progestins medroxyprogesterone acetate and megestrol acetate has been obtained in postmenopausal patients with advanced breast cancer. However, extensive information on the effect of progestins was obtained in in vitro studies using hormone-dependent and hormone-independent human mammary cancer cell lines. It was demonstrated that in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) as well as tibolone, are potent sulfatase-inhibitory agents. Progestins may also be involved in the inhibition of the mRNA of this enzyme. In another series of studies, it was also demonstrated that various progestins are very active in inhibiting the 17 beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently, it has been observed that promegestone or medrogestone stimulates the sulfotransferase for the formation of estrogen sulfates. Clinical trials of these enzymatic effects on the formation and transformation of estradiol in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
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PMID:Biological effects of progestins in breast cancer. 1222 97

Sperm acrosome reaction (AR) is a prerequisite step for in vivo fertilization. In the vicinity of the oocyte, zona protein(s) (ZP) and progesterone (P4), a component of follicular fluid, are proven to be responsible for physiological AR induction. In the present study, a thorough analysis of the role of the progesterone receptor (PR) in this processing including in vitro physiological studies and biochemical isolation and characterization of the receptor protein was conducted. Following capacitation for 0, 2, 4 and 6h, pooled fertile boar semen samples (n=6) with >70% sperm motility were labeled with P4-BSA-FITC (100 microg/ml) to detect the activation of PR. Parallel sperm samples were treated with P4 (10 microg/ml) for 20 min to test AR inducing efficiency at different time points. To compare the ability of ZP and P4 to induce AR, spermatozoa capacitated in a modified medium supplemented with 1mg/ml heparin for 4h, were then treated with heat solubilized ZP (150 microg/ml), P4 (10 microg/ml) or ZP+P4 for 20 min. FITC-peanut agglutinin staining was applied to observe the disrupt acrosomal morphology. A purification protocol for crude boar sperm membrane proteins was developed based on ligand-receptor affinity chromatography procedures. The PR proteins were then identified by using mAb C262 raised against intracellular PR, combined with second antibody (SDS-PAGE, Western blotting). Their N-terminal amino acid sequence was determined. The amount of PR-activated spermatozoa was enhanced with time (onset: 27+/-5%, 2h: 41+/-4%, 4h: 49+/-3% and 6h: 52+/-4%, mean+/-S.E., n=6) as evidenced by increasing percentage of spermatozoa with completed cap fluorescent staining. In parallel sperm samples, percentages of AR induced by P4 were 9+/-2, 14+/-2, 18+/-2, and 24+/-2%, respectively. In solvent control at all time points, less than 10% spermatozoa had undergone AR. Capacitation for 4h or greater time periods resulted in optimal percentage of PR-activated and acrosome-reacted spermatozoa. After sperm incubation in heparin-medium, ZP+P4 treatment induced greater amounts of AR than either P4 or ZP alone (13+/-1% compared with 8+/-1 and 10+/-1%, P<0.01). Inducing capacity of P4 was comparable to that of ZP. The molecule weights of two apparent PR molecular masses were detected to be at Mr 74 kDa and Mr 63 kDa. N-terminal amino acid sequence of 74 kDa protein was XPXNIVLIFADXLXY, which had 78% homology to arylsulfatase A and 88% homology to 72 kDa protein from boar spermatozoa. The activation of PR is associated with the capacitating process and that appears to be required for P4-induced AR. P4 and ZP appear to be equally capable of independently inducing the AR but lack synergetic or additive effects in this induction process. Both might represent alternative pathways thus resulting in alternative systems for induction of the prerequisite acrosomal exocytosis (supported by NSC 90-2313-B-005-114; 91-2313-B-005-131).
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PMID:Expression of progesterone receptor(s) during capacitation and incidence of acrosome reaction induced by progesterone and zona proteins in boar spermatozoa. 1613 44


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