Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen-regulated gene expression in MCF-7 cells: Up-regulation of oestrogen receptor beta

Barker, Stewart; Malouitre, S. D. M.; Glover, Hilary R.; Puddefoot, J. R.; Vinson, Gavin P.

doi:10.1016/j.jsbmb.2006.04.006

Cited by 11 publications

(15 citation statements)

References 48 publications

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“…In addition, a concentrationdependent inhibition of 17β-estradiol-stimulated EREreporter activity in both MCF-7 and T-47D breast cancer cells by trilostane, with a threshold inhibition at 1 μM trilostane, an action similar to that of tamoxifen, which also inhibits 17β-estradiol-dependent ERE-reporter activity (Weatherman and Scanlan 2001). Moreover, in a comparative study of the effects of 4-hydroxy-tamoxifen and trilostane, in the presence of 17β-estradiol on gene expression in MCF-7 breast cancer cells using microarrays, the same authors observed selective up-regulation of ERβ by trilostane, but not 4-hydroxy-tamoxifen (Barker et al 2006). The authors particularly propose that trilostane-specific up-regulation of ERβ could explain its positive benefit rates in acquired tamoxifen resistance (Barker et al 2006).…”

Section: Discussionmentioning

confidence: 87%

“…Moreover, in a comparative study of the effects of 4-hydroxy-tamoxifen and trilostane, in the presence of 17β-estradiol on gene expression in MCF-7 breast cancer cells using microarrays, the same authors observed selective up-regulation of ERβ by trilostane, but not 4-hydroxy-tamoxifen (Barker et al 2006). The authors particularly propose that trilostane-specific up-regulation of ERβ could explain its positive benefit rates in acquired tamoxifen resistance (Barker et al 2006).…”

Section: Discussionmentioning

confidence: 95%

“…Trilostane inhibited ER-mediated stimulation of cell proliferation and transcriptional activation in cell-based reporter assays through a quite different mechanism from that reported for other known ER antagonists (Puddefoot et al 2002). Trilostane-specific up-regulation of ERβ could explain its positive benefit rates in acquired tamoxifen resistance (Barker et al 2006). Trilostane is therefore a steroid with putative direct effects on ERβ, acting without displacing estradiol from, or competing with estradiol for, binding to ERβ ligand binding domain (Puddefoot et al 2002).…”

mentioning

confidence: 83%

“…It caused a shift in binding preference of estradiol from ERα to favor binding to ERβ. In addition, there is a concentration-dependent inhibition of estrogen-stimulated ERE-reporter activity by trilostane, with a threshold inhibition at 1 μM trilostane (Barker et al 2006).…”

mentioning

confidence: 99%

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The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors

Espallergues

Temsamani²,

Laruelle³

et al. 2010

Psychopharmacology

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 83%

mentioning

confidence: 99%

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The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors

Espallergues

Temsamani²,

Laruelle³

et al. 2010

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…Extending these concepts, Barker et al have shown that in rats, 7-day treatment with trilostane 4 mg/kg/day produces an increase in the ratio of ER-β to ER-α, but does not result in increased overall expression of ER in the uteri of treated animals [22]. Gene arrays highlight the difference in the mode of action of trilostane and tamoxifen.…”

Section: Trilostane: Novel Mode Of Actionmentioning

confidence: 99%

Trilostane in advanced breast cancer

Puddefoot

Barker

Vinson

2006

Expert Opinion on Pharmacotherapy

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Antiestrogens, principally tamoxifen, and aromatase inhibitors have been used as the first- and second-line therapy in patients with advanced postmenopausal breast cancer for many years. However, some patients acquire resistance to these treatments and, at present, further endocrine treatment is achieved by merely substituting the current medication with a different antiestrogen or aromatase inhibitor. Trilostane offers an alternative endocrine treatment due to its unique mode of action. It is an allosteric modulator of the estrogen receptor and targets both the estrogen- and growth factor-dependent pathways through which estradiol stimulates cell proliferation. In clinical trials, trilostane has been shown to be an effective treatment for breast cancer in patients who have relapsed after receiving treatment with one or more forms of endocrine therapy. Ongoing and future clinical trials are examining the potential for the use of trilostane in premenopausal breast cancer, as well as in other malignancies such as prostate cancer.

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Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons

2009

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Although androgens induce numerous actions in brain, relatively little is known about which cell signaling pathways androgens activate in neurons. Recent work in our laboratory showed that the androgens testosterone and dihydrotestosterone (DHT) activate androgen receptor (AR)-dependent mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling. Since the transcription factor cyclic AMP response element binding protein (CREB) is a downstream effector of MAPK/ERK and androgens activate and CREB in non-neuronal cells, we investigated whether androgens activate CREB signaling in neurons. First, we observed that DHT rapidly activates CREB in cultured hippocampal neurons, as evidenced by CREB phosphorylation. Further, we observed that DHT-induced CREB phosphorylation is AR-dependent, as it occurs in PC12 cells stably transfected with AR but in neither wild-type nor empty vector-transfected cells. Next, we sought to identify the signal transduction pathways upstream of CREB phosphorylation using pharmacological inhibitors. DHT-induced CREB phosphorylation in neurons was found to be dependent upon protein kinase C (PKC) signaling but independent of MAPK/ERK, phosphatidylinositol 3-kinase, protein kinase A, and Ca 2+ /calmodulin-dependent protein kinase IV. These results demonstrate that DHT induces PKC-dependent CREB signaling, which may contribute to androgen-mediated neural functions.

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Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen-regulated gene expression in MCF-7 cells: Up-regulation of oestrogen receptor beta

Cited by 11 publications

References 48 publications

The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors

The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors

Trilostane in advanced breast cancer

Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons

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