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Estrogen and androgen-converting enzymes 17 beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17 beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 18, 30552-30562 p.Article, review/survey (Refereed) Published
Abstract [en]

Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17 beta-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-a, responsible for promoting the growth of the tissue. Further, 60-80% express the androgen receptor, which has been shown to have tissue protective effects in estrogen receptor positive breast cancer, and a more ambiguous response in estrogen receptor negative breast cancers. In this review, we summarize the function and clinical relevance in cancer for 17 beta-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3 alpha- and 3 beta-diol as well as 17 beta-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17 beta-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17 beta-hydroxysteroid dehydrogenases 1 has been proposed to be a prime candidate for inhibition in patients who develop aromatase inhibitor resistance or in combination with aromatase inhibitors as a first line treatment. Here we review the status of inhibitors against 17 beta-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17 beta-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2017. Vol. 8, no 18, 30552-30562 p.
Keyword [en]
breast cancer; estrogens; androgens; HSD17B1; HSD17B2
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-137841DOI: 10.18632/oncotarget.15547ISI: 000400456200081PubMedID: 28430630OAI: oai:DiVA.org:liu-137841DiVA: diva2:1105164
Note

Funding Agencies|Swedish Cancer Society [150349]

Available from: 2017-06-02 Created: 2017-06-02 Last updated: 2017-06-02

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Hilborn, ErikStål, OlleJansson, Agneta
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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