Testosterone and 5α-dihydrotestosterone inhibit<i>in vitro</i>growth of human breast cancer cell lines

Ortmann, J.; Prifti, S.; Bohlmann, Michael K.; Rehberger-Schneider, S.; Strowitzki, Thomas; Rabe, T.

doi:10.1080/gye.16.2.113.120

Cited by 71 publications

(14 citation statements)

References 20 publications

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“…Currently, controversy exists as to the significance of androgenic effects in breast cancer, and therefore, by extension, the importance of local DHEA sulfation and desulfation. Unlike estrogens, in normal breast androgens inhibit proliferation ( 292 , 293 ). However, in breast cancer, androgenic effects are complex and most likely depend on the differing intracrinology of different breast carcinomas (see Ref.…”

Section: Dysregulation Of Steroid Sulfation and Desulfationmentioning

confidence: 99%

The Regulation of Steroid Action by Sulfation and Desulfation

et al. 2015

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Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.

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Section: Dysregulation Of Steroid Sulfation and Desulfationmentioning

confidence: 99%

The Regulation of Steroid Action by Sulfation and Desulfation

et al. 2015

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“…Studies of the effect of androgens on cell proliferation have generated conflicting results. Inhibition of proliferation has been reported often, in normal and cancer cell lines from a range of tissues, either naturally expressing or transduced with AR [ 25 – 40 ]. No change or an increase in cell proliferation has also been reported [ 34 , 40 – 43 ].…”

Section: Discussionmentioning

confidence: 99%

Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro

2017

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BackgroundWe showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer.AimTo investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro.Methods and ResultsIn tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation.ConclusionsThis is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.Electronic supplementary materialThe online version of this article (doi:10.1007/s10620-017-4794-5) contains supplementary material, which is available to authorized users.

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“…To study the effects of androgens and AR/ Ar on diverse cell culture systems and the relevance for cell biology, cell culture experiments were conducted in different human cell lines (e.g. breast cancer cells, adrenocortical carcinoma cells, murine skeletal muscle cells or liver carcinoma cells [ 9 – 12 ]). Also AR-deficient cell lines have been used, either transfected with AR [ 14 , 15 ] or without [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…To examine the role of the AR/ Ar in different biological processes such as cell growth and survival as well as AR/ Ar -dependent gene expression, cell culture systems are needed. Therefore, administration of T and/or the more efficient metabolite DHT has widely been used to investigate the effect of androgens and AR/ Ar , respectively, in diverse cultured cells such as human breast cancer cells, adrenocortical carcinoma cells, murine skeletal muscle cells or liver carcinoma cells [ 9 – 12 ]. Additionally, AR/ Ar -deficient cell lines were used, e.g.…”

Section: Introductionmentioning

confidence: 99%

Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation

et al. 2015

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BackgroundAndrogens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell culture systems and AR-transfected cell lines are needed. Transfection of AR into cell lines and subsequent gene expression analysis after androgen treatment is well established to investigate the molecular biology of target cells. However, it remains unclear how the transfection with AR itself can modulate the gene expression even without androgen stimulation. Therefore, we transfected Ar-deficient rat Sertoli cells 93RS2 by electroporation using a full length human AR.ResultsTransfection success was confirmed by Western Blotting, immunofluorescence and RT-PCR. AR transfection-related gene expression alterations were detected with microarray-based genome-wide expression profiling of transfected and non-transfected 93RS2 cells without androgen stimulation. Microarray analysis revealed 672 differentially regulated genes with 200 up- and 472 down-regulated genes. These genes could be assigned to four major biological categories (development, hormone response, immune response and metabolism). Microarray results were confirmed by quantitative RT-PCR analysis for 22 candidate genes.ConclusionWe conclude from our data, that the transfection of Ar-deficient Sertoli cells with AR has a measurable effect on gene expression even without androgen stimulation and cause Sertoli cell damage. Studies using AR-transfected cells, subsequently stimulated, should consider alterations in AR-dependent gene expression as off-target effects of the AR transfection itself.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-015-0051-7) contains supplementary material, which is available to authorized users.

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Testosterone and 5α-dihydrotestosterone inhibitin vitrogrowth of human breast cancer cell lines

Cited by 71 publications

References 20 publications

The Regulation of Steroid Action by Sulfation and Desulfation

The Regulation of Steroid Action by Sulfation and Desulfation

Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro

Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation

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