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The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors

The extragonadal synthesis of biological active steroid hormones from their inactive precursors in target tissues is named “intracrinology.” Of particular importance for the progression of estrogen-dependent cancers is the in situ formation of the biological most active estrogen, 17beta-estradiol (E...

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Autores principales: Secky, Lena, Svoboda, Martin, Klameth, Lukas, Bajna, Erika, Hamilton, Gerhard, Zeillinger, Robert, Jäger, Walter, Thalhammer, Theresia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586502/
https://www.ncbi.nlm.nih.gov/pubmed/23476785
http://dx.doi.org/10.1155/2013/957605
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author Secky, Lena
Svoboda, Martin
Klameth, Lukas
Bajna, Erika
Hamilton, Gerhard
Zeillinger, Robert
Jäger, Walter
Thalhammer, Theresia
author_facet Secky, Lena
Svoboda, Martin
Klameth, Lukas
Bajna, Erika
Hamilton, Gerhard
Zeillinger, Robert
Jäger, Walter
Thalhammer, Theresia
author_sort Secky, Lena
collection PubMed
description The extragonadal synthesis of biological active steroid hormones from their inactive precursors in target tissues is named “intracrinology.” Of particular importance for the progression of estrogen-dependent cancers is the in situ formation of the biological most active estrogen, 17beta-estradiol (E2). In cancer cells, conversion of inactive steroid hormone precursors to E2 is accomplished from inactive, sulfated estrogens in the “sulfatase pathway” and from androgens in the “aromatase pathway.” Here, we provide an overview about expression and function of enzymes of the “sulfatase pathway,” particularly steroid sulfatase (STS) that activates estrogens and estrogen sulfotransferase (SULT1E1) that converts active estrone (E1) and other estrogens to their inactive sulfates. High expression of STS and low expression of SULT1E1 will increase levels of active estrogens in malignant tumor cells leading to the stimulation of cell proliferation and cancer progression. Therefore, blocking the “sulfatase pathway” by STS inhibitors may offer an attractive strategy to reduce levels of active estrogens. STS inhibitors either applied in combination with aromatase inhibitors or as novel, dual aromatase-steroid sulfatase inhibiting drugs are currently under investigation. Furthermore, STS inhibitors are also suitable as enzyme–based cancer imaging agents applied in the biomedical imaging technique positron emission tomography (PET) for cancer diagnosis.
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spelling pubmed-35865022013-03-09 The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors Secky, Lena Svoboda, Martin Klameth, Lukas Bajna, Erika Hamilton, Gerhard Zeillinger, Robert Jäger, Walter Thalhammer, Theresia J Drug Deliv Review Article The extragonadal synthesis of biological active steroid hormones from their inactive precursors in target tissues is named “intracrinology.” Of particular importance for the progression of estrogen-dependent cancers is the in situ formation of the biological most active estrogen, 17beta-estradiol (E2). In cancer cells, conversion of inactive steroid hormone precursors to E2 is accomplished from inactive, sulfated estrogens in the “sulfatase pathway” and from androgens in the “aromatase pathway.” Here, we provide an overview about expression and function of enzymes of the “sulfatase pathway,” particularly steroid sulfatase (STS) that activates estrogens and estrogen sulfotransferase (SULT1E1) that converts active estrone (E1) and other estrogens to their inactive sulfates. High expression of STS and low expression of SULT1E1 will increase levels of active estrogens in malignant tumor cells leading to the stimulation of cell proliferation and cancer progression. Therefore, blocking the “sulfatase pathway” by STS inhibitors may offer an attractive strategy to reduce levels of active estrogens. STS inhibitors either applied in combination with aromatase inhibitors or as novel, dual aromatase-steroid sulfatase inhibiting drugs are currently under investigation. Furthermore, STS inhibitors are also suitable as enzyme–based cancer imaging agents applied in the biomedical imaging technique positron emission tomography (PET) for cancer diagnosis. Hindawi Publishing Corporation 2013 2013-02-13 /pmc/articles/PMC3586502/ /pubmed/23476785 http://dx.doi.org/10.1155/2013/957605 Text en Copyright © 2013 Lena Secky et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Secky, Lena
Svoboda, Martin
Klameth, Lukas
Bajna, Erika
Hamilton, Gerhard
Zeillinger, Robert
Jäger, Walter
Thalhammer, Theresia
The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title_full The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title_fullStr The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title_full_unstemmed The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title_short The Sulfatase Pathway for Estrogen Formation: Targets for the Treatment and Diagnosis of Hormone-Associated Tumors
title_sort sulfatase pathway for estrogen formation: targets for the treatment and diagnosis of hormone-associated tumors
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586502/
https://www.ncbi.nlm.nih.gov/pubmed/23476785
http://dx.doi.org/10.1155/2013/957605
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