3,903 research outputs found
Precision nanomedicines for prostate cancer
No full textEditorial. Published online: 27 February 2018Anna Cifuentes-Rius, Lisa M Butler and Nicolas H Voelcke
Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Delta(4)-tibolone
No full textData source: Supplementary material, http://www.sciencedirect.com/science/article/pii/S0303720713004747#appd002Abstract not availableTina Bianco-Miotto, Andrew P. Trotta, Eleanor F. Need, Alice M.C. Lee, Aleksandra M. Ochnik,, Lauren Giorgio, Damien A. Leach, Erin E. Swinstead, Melissa A. O’Loughlin, Michelle R. Newman, Stephen N. Birrell, Lisa M. Butler, Jonathan M.Harris, Grant Buchana
The Contribution of Different Androgen Receptor Domains to Receptor Dimerization and Signaling
No full textThe androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5{alpha}-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.Margaret M. Centenera, Jonathan M. Harris, Wayne D. Tilley and Lisa M. Butle
Prostate cell lines as models for biomarker discovery: performance of current markers and the search for new biomarkers
No full textAbstract not availableIan R. Johnson, Emma J. Parkinson-Lawrence, Lisa M. Butler, and Doug A. Brook
Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer
No full textCopyright © 2007 by The Federation of American Societies for Experimental BiologyThere is now considerable evidence that using a combination of synthetic progestins and estrogens in hormone replacement therapy (HRT) increases the risk of breast cancer compared with estrogen alone. Furthermore, the World Health Organization has recently cited combination contraceptives, which contain synthetic progestins, as potentially carcinogenic to humans, particularly for increased breast cancer risk. Given the above observations and the current trend toward progestin-only contraception, it is important that we have a comprehensive understanding of how progestins act in the millions of women worldwide who regularly take these medications. While synthetic progestins, such as medroxyprogesterone acetate (MPA), which are currently used in both HRT and oral contraceptives were designed to act exclusively through the progesterone receptor, it is clear from both clinical and experimental settings that their effects may be mediated, in part, by binding to the androgen receptor (AR). Disruption of androgen action by synthetic progestins may have serious deleterious side effects in the breast, where the balance between estrogen signaling and androgen signaling plays a critical role in breast homeostasis. Here, we review the role of androgen signaling in the normal breast and in breast cancer and present new data demonstrating that androgen receptor function can be perturbed by low doses of MPA, similar to doses achieved in serum of women taking HRT. We propose that the observed excess of breast malignancies associated with combined HRT may be explained, in part, by synthetic progestins such as MPA acting as endocrine disruptors to negate the protective effects of androgen signaling in the breast. Understanding the role of androgen signaling in the breast and how this is modulated by synthetic progestins is necessary to determine how combined HRT alters breast cancer risk, and to inform the development of optimal preventive and treatment strategies for this disease.Stephen N. Birrell, Lisa M. Butler, Jonathan M. Harris, Grant Buchanan and Wayne D. Tille
Functional Androgen Signaling in an Explant Model of Normal Human Breast Tissue.
No full textSubmitted abstractTheresa E. Hickey, Aleksandra Ocknik, Tina Bianco-Miotto, Steve N. Birrell, Lisa M. Butler, Wayne D. Tille
Molecular pathology and prostate cancer therapeutics: from biology to bedside
No full textArticle first published online: 10 DEC 2013Abstract not availableDaniel Nava Rodrigues, Lisa M Butler, David Lorente Estelles and Johann S de Bon
New Opportunities for Targeting the Androgen Receptor in Prostate Cancer
No full textRecent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies.Margaret M. Centenera, Luke A. Selth, Esmaeil Ebrahimie, Lisa M. Butler and Wayne D. Tille
Author correction: obesity and ethnicity alter gene expression in skin
No full textDaniel Butler was omitted from the author list in the original version of this Article. The Author contributions section now reads: “J.M.W. designed, conducted, and contributed to the writing of the manuscript, prepared Fig. 1. S.G. evaluated and did statistical analysis on the skin and fat samples, prepared Figs. 2–9. J.O.A. evaluated and contributed to writing the manuscript. D.B prepared and sequenced DNA libraries for the skin microbiota data, and wrote the applicable parts of the methods section. C.M. analyzed and wrote up the skin microbiota data, prepared Fig. 10. All authors have read the manuscript and approved its contents. D.D. analyzed and wrote up the skin microbiota data. S.Z. ran and analyzed the skin metabolite data. J.S. assisted in design, analysis and wrote up the skin metabolite data. J.K. assisted in analysis write up of skin and fat data. J.L.B. assisted in analysis, interpretation and writing of the manuscript. P.R.H. designed, analyzed, interpreted the data, and was the primary author of the manuscript.” This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.</p
Androgenic regulation of lipid elongation in prostate cancer
No full textAbstractZeyad D Nassar, Margaret M Centenera, Jelle Machiels, Samuel J Polacek, Katarzyna Bloch, Wayne D Tilley, Luke A Selth, Lisa M Butler, and Johannes V Swinne
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