Expression of estrogen sulfotransferase in MCF-7 cells by cDNA transfection suppresses the estrogen response: potential role of the enzyme in regulating estrogen-dependent growth of breast epithelial cells.

Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the sulfonation of estrogens at the 3-hydroxyl position by use of 3'-phosphoadenosine-5'-phosphosulfate as an activated sulfate donor. Although largely known and studied as a phase II metabolic enzyme with prominent expression in the liver, the high substrate specificity of EST (with a high Vmax/Km value for estrogen) suggests that expression of the enzyme in extrahepatic, estrogen target tissues, such as the breast epithelium, may constitute an effective mechanism for local estrogen regulation as well. In this study, we have evaluated the physiological significance of EST expression by cDNA transfection studies with use of the estrogen-dependent MCF-7 breast cancer cell line as a model system. We show that expression of EST in MCF-7 cells effectively reduces the cells' response to physiological concentrations of estradiol (10 nM) by up to 70% as determined in an estrogen-responsive reporter gene assay. In addition, we demonstrate that expression of EST similarly inhibits estrogen-stimulated DNA synthesis and cell proliferation by 21% and 46%, respectively. (The thymidine incorporation rate was measured 3 days after and the cell numbers were counted 8 days after transfection.) These results provide direct evidence for the functional significance of in situ EST expression in the breast epithelium and suggest that abnormal regulation of the enzyme may have pathological implications in the development and maintenance of hormone-dependent breast carcinomas.

• Publication year

  1998

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1998-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0022-3565(24)37617-7PMID 9655902
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Aromatase inhibitors — mechanisms of steroidal inhibitors

  2004cited by this paper
• Estrogen sulfotransferase expression in the human liver: marked interindividual variation and lack of gender specificity.

  1998cited by this paper
• Mouse steroid sulfotransferases: substrate specificity and preliminary X-ray crystallographic analysis.

  1998influential reference
• Inhibition of estrone sulfatase and proliferation of human breast cancer cells by nonsteroidal (p-O-sulfamoyl)-N-alkanoyl tyramines.

  1997influential reference
• Molecular endocrinology of hydroxysteroid dehydrogenases.

  1997cited by this paper
• Enzymology of human cytosolic sulfotransferases

  1997cited by this paper
• Sulfotransferase molecular biology: cDNAs and genes

  1997cited by this paper
• Estrogenic responses in estrogen receptor-alpha deficient mice reveal a distinct estrogen signaling pathway.

  1997cited by this paper
• Steroid sulfotransferases.

  1996cited by this paper
• Cloning of a novel receptor expressed in rat prostate and ovary.

  1996cited by this paper
• Expression of cytosolic sulfotransferases in normal mammary epithelial cells and breast cancer cell lines.

  1996influential reference
• Steroid sulfotransferases.

  1996cited by this paper
• Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase.

  1995cited by this paper
• Molecular characterization of a testis-specific estrogen sulfotransferase and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db mice.

  1995influential reference
• Inactivation of steroid sulfatase by an active site-directed inhibitor, estrone-3-O-sulfamate.

  1995cited by this paper
• Steroid sulfation by expressed human cytosolic sulfotransferases.

  1994cited by this paper
• Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis.

  1994cited by this paper
• Current perspectives on aromatase inhibitors in breast cancer.

  1994cited by this paper
• COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene

  1993cited by this paper
• Inhibition of estrone sulfatase activity by estrone-3-methylthiophosphonate: a potential therapeutic agent in breast cancer.

  1993cited by this paper
• Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer.

  1992influential reference
• Steroid sulphotransferase activity in human hormone-independent MDA-MB-468 mammary cancer cells.

  1992influential reference
• Sulfation of estrone and 17 beta-estradiol in human liver. Catalysis by thermostable phenol sulfotransferase and by dehydroepiandrosterone sulfotransferase.

  1992cited by this paper
• Regulation of Steroid Hormone Action in Target Cells by Specific Hormone-Inactivating Enzymes

  1992influential reference
• Control of human breast cancer by estrogen, growth factors, and oncogenes.

  1988cited by this paper
• Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated.

  1988cited by this paper
• Endocrine steroid sulfotransferases: steroid alcohol sulfotransferase from human breast carcinoma cell line MCF-7.

  1986cited by this paper
• Steroid sulfotransferases and steroid sulfate sulfatases: characteristics and biological roles.

  1985cited by this paper
• [Steroid hormone receptors in breast cancer].

  1984cited by this paper
• Steroid‐hormone receptors in breast cancer

  1984cited by this paper
• Estrogen sulfatase and estrogen sulfotransferase in human primary mammary carcinoma.

  1983influential reference
• Estrogen sulfurylation as an alternative indicator of hormone dependence in human breast cancer.

  1982influential reference
• Conjugation of androgens and estrogens by human breast tumors in vitro.

  1980cited by this paper
• Multiple hormone interactions in the developmental biology of the mammary gland.

  1980cited by this paper
• A correlation between estrogen sulfotransferase levels and estrogen receptor status in human primary breast carcinoma.

  1979cited by this paper
• Role of sulfate conjugation in estrogen metabolism and activity.

  1978cited by this paper
• The steroid alcohol and estrogen sulfotransferases in rodent and human mammary tumors.

  1975cited by this paper
• Studies on steroic sulphation and binding by human malignant tumours.

  1974cited by this paper
• Predictability of response to endocrine ablation in advanced breast carcinoma. A correlation to estrogen receptor and steroid sulfurylation.

  1973cited by this paper
• Estrogen receptors in human breast cancer.

  1973cited by this paper
• Cloning of a novel estrogen receptor expressed in rat prostate and ovary

  year unknowncited by this paper

• Metabolic Messengers: oestradiol

  2025cites this paper
• A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment

  2024cites this paper
• Estrogen sulfotransferase SULT1E1 expression levels and regulated factors in malignant tumours.

  2023cites this paper
• HUMAN ESTROGEN SULFOTRANSFERASE (EST) ENZYME MODULATES MAPK PATHWAY IN HUMAN BREAST CANCER CELL LINE MCF-7

  2021influential citation
• A high-throughput cell-based assay pipeline for the preclinical development of bacterial DsbA inhibitors as antivirulence therapeutics

  2021cites this paper
• SULT genetic polymorphisms: physiological, pharmacological and clinical implications

  2021cites this paper
• Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives

  2021cites this paper
• Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure

  2020cites this paper
• Impact of Human SULT1E1 Polymorphisms on the Sulfation of 17β-Estradiol, 4-Hydroxytamoxifen, and Diethylstilbestrol by SULT1E1 Allozymes

  2020cites this paper
• The potential disruption of estrogen and androgen homeostasis and adipocyte differentiation by metabolites of common airborne polychlorinated biphenyls

  2019cites this paper
• Development and validation of LC-ESI-MS/MS methods for quantification of 27 free and conjugated estrogen-related metabolites.

  2019cites this paper
• Inherited Variants in SULT1E1 and Response to Abiraterone Acetate by Men with Metastatic Castration Refractory Prostate Cancer.

  2016cites this paper
• THE EFFECT OF QUERCETIN ON PLASMA GONADOTROPIN AND STEROID HORMONES IN RATS EXPOSED TO BISPHENOL A

  2015cites this paper
• Biotransformation of endocrine disrupting compounds by selected phase I and phase II enzymes--formation of estrogenic and chemically reactive metabolites by cytochromes P450 and sulfotransferases.

  2014cites this paper
• The Role of Estrogen Sulfotransferase in Human Adipogenesis

  2014cites this paper
• Interactions of Endoxifen and other major metabolites of Tamoxifen with human sulfotransferases SULT2A1, SULT1E1, and SULT1A1*1 : implications for the therapeutic action and toxicity of Tamoxifen

  2014cites this paper
• Impact of cows’ milk estrogen on cancer risk

  2012cites this paper
• Biomarkers of endocrine disruption: cluster analysis of effects of plasticisers on Phase 1 and Phase 2 metabolism of steroids.

  2012cites this paper
• Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications

  2012cites this paper
• Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer

  2011cites this paper
• Steroid sulfatase and estrogen sulfotransferase in human carcinomas.

  2011cites this paper
• Estrogen sulfotransferase (sult1e1) expression and function in mcf10a-series breast epithelial cells: role as a modifier of breast carcinogenesis and regulation by proliferation state

  2011cites this paper
• Inhibition of cortisol metabolism by 17alpha,20beta-P: mechanism mediating semelparity in salmon?

  2010cites this paper
• The role of biotransformation in the estrogenicity of xenobiotics

  2010cites this paper
• The role of biotransformation in the estrogenicity of xenobiotics

  2010cites this paper
• The role of biotransformation in the estrogenicity of xenobiotics

  2010cites this paper
• The role of biotransformation in the estrogenicity of xenobiotics

  2010cites this paper
• Comparison of murine and human estrogen sulfotransferase inhibition in vitro and in silico--implications for differences in activity, subunit dimerization and substrate inhibition.

  2010cites this paper
• The human estrogen sulfotransferase: a half-site reactive enzyme.

  2010cites this paper
• Estrogen Sulfotransferases in Breast and Endometrial Cancers

  2009cites this paper
• Sulfotransferase in Adipose Tissues of the Mouse Gender-Specific Expression and Mechanism of Regulation of Estrogen

  2008cites this paper
• Phytoestrogens and xenoestrogens: the contribution of diet and environment to endocrine disruption.

  2008cites this paper
• Transfection of Human Prostate Cancer CA-HPV-10 Cells with Cytosolic Sulfotransferase SULT1E1 Affects Estrogen Signaling and Gene Transcription

  2008cites this paper
• Gender-specific expression and mechanism of regulation of estrogen sulfotransferase in adipose tissues of the mouse.

  2008cites this paper
• Inhibitory effects of various beverages on the sulfoconjugation of 17beta-estradiol in human colon carcinoma Caco-2 cells.

  2008cites this paper
• Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase.

  2008cites this paper
• Estrogen deprivation and inhibition of breast cancer growth in vivo through activation of the orphan nuclear receptor liver X receptor.

  2007cites this paper
• Effects of Endocrine Disruptors on Dehydroepiandrosterone Sulfotransferase and Enzymes Involved in PAPS Synthesis: Genomic and Nongenomic Pathways

  2007cites this paper
• Correlation of estrogen sulfotransferase activity and proliferation in normal and carcinomatous human breast. A hypothesis.

  2007cites this paper
• The Role of Estrogen Sulfotransferase in Leydig Cells

  2007cites this paper
• Development and validation of a fluorescence HPLC-based screening assay for inhibition of human estrogen sulfotransferase.

  2006cites this paper
• Selective spatial upregulation of intratumoral stromal aromatase in breast cancer patients: evidence for imbalance of local estrogen metabolism.

  2006influential citation
• Cytosolic sulfotransferases.

  2006cites this paper
• Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer.

  2005cites this paper
• Non-genomic effects of endocrine disrupters: inhibition of estrogen sulfotransferase by phenols and chlorinated phenols.

  2005cites this paper
• Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferase—deficient mice

  2005cites this paper
• Production in Human Thymoma In situ Estrogen Inhibits Cell Proliferation through

  2005cites this paper
• Estrogen Inhibits Cell Proliferation through In situ Production in Human Thymoma

  2005cites this paper
• Sulfotransferase 2A1 forms estradiol-17-sulfate and celecoxib switches the dominant product from estradiol-3-sulfate to estradiol-17-sulfate.

  2005cites this paper
• Estrogen Sulfotransferase in Breast Cancer

  2005cites this paper
• Breast cancer, estrogen, soy genistein, and other dietary factors

  2005cites this paper
• Sex steroid-producing enzymes in human breast cancer.

  2005cites this paper
• The selective estrogen enzyme modulators in breast cancer: a review.

  2004cites this paper
• Sulfotransferases: structure, mechanism, biological activity, inhibition, and synthetic utility.

  2004cites this paper
• Aberrant cholesterol transport and impaired steroidogenesis in Leydig cells lacking estrogen sulfotransferase.

  2004cites this paper
• Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment.

  2004cites this paper
• Endokrinologie der Phytoöstrogene

  2003cites this paper
• Inhibition of rat liver sulfotransferases SULT1A1 and SULT2A1 and glucuronosyltransferase by dietary flavonoids

  2003cites this paper
• Chapter 20. Beyond kinases: Purine-binding enzymes as cancer targets

  2003cites this paper
• Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics

  2003cites this paper
• Differential effects of progestins on breast tissue enzymes.

  2003cites this paper
• Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma.

  2003cites this paper
• Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma.

  2003cites this paper
• Sulfonation and molecular action.

  2002cites this paper
• In situ production of estrogens in human breast carcinoma

  2002cites this paper
• Regulation of MCF-7 breast cancer cell growth by beta-estradiol sulfation.

  2002cites this paper
• Regulation of MCF-7 Breast Cancer Cell Growth by β-estradiol Sulfation

  2002influential citation
• Dual effects of phytoestrogens result in u-shaped dose-response curves.

  2002cites this paper
• A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors.

  2001cites this paper
• Glutathione Stimulates Sulfated Estrogen Transport by Multidrug Resistance Protein 1*

  2001cites this paper
• A helical lid converts a sulfotransferase to a dehydratase

  2001cites this paper
• Do dietary phytoestrogens influence susceptibility to hormone-dependent cancer by disrupting the metabolism of endogenous oestrogens?

  2001cites this paper
• The selective estrogen enzyme modulator (SEEM) in breast cancer.

  2001cites this paper
• Discovery of estrogen sulfotransferase inhibitors from a purine library screen.

  2001cites this paper
• Biochemistry and Reproductive Endocrinology of Estrogen Sulfotransferase

  2001cites this paper
• Sulfation of “Estrogenic” Alkylphenols and 17β-Estradiol by Human Platelet Phenol Sulfotransferases*

  2000cites this paper
• SULT1A1 catalyzes 2-methoxyestradiol sulfonation in MCF-7 breast cancer cells.

  2000cites this paper
• Steroid transformation enzymes as critical regulators of steroid action in vivo.

  2000cites this paper
• Quercetin and resveratrol potently reduce estrogen sulfotransferase activity in normal human mammary epithelial cells.

  2000cites this paper
• Correlation between PAP-dependent steroid binding activity and substrate specificity of mouse and human estrogen sulfotransferases.

  1999cites this paper
• Regulation of estrogen sulfotransferase expression in Leydig cells by cyclic adenosine 3',5'-monophosphate and androgen.

  1999cites this paper