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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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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. |
format | Online Article Text |
id | pubmed-3586502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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