Estrogen and androgen-converting enzymes 17beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer.
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Hilborn E, Stal O, Jansson A
Estrogen and androgen-converting enzymes 17beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer.
Oncotarget. 2017 May 2;8(18):30552-30562. doi: 10.18632/oncotarget.15547.
- PubMed ID
- 28430630 [ View in PubMed]
- Abstract
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 17beta-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-alpha, 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 17beta-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3alpha- and 3beta-diol as well as 17beta-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17beta-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17beta-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 17beta-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17beta-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Prasterone Estradiol 17-beta-dehydrogenase 1 Protein Humans UnknownSubstrateDetails