دورية أكاديمية
Androgen receptor mutations modulate activation by 11-oxygenated androgens and glucocorticoids.
العنوان: | Androgen receptor mutations modulate activation by 11-oxygenated androgens and glucocorticoids. |
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المؤلفون: | Snaterse G; Department of Internal Medicine, Section of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Mies R; Department of Internal Medicine, Section of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., van Weerden WM; Department of Urology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., French PJ; Cancer Treatment Screening Facility, Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Jonker JW; Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Houtsmuller AB; Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., van Royen ME; Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Visser JA; Department of Internal Medicine, Section of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands., Hofland J; Department of Internal Medicine, Section of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. j.hofland@erasmusmc.nl. |
المصدر: | Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2023 Jun; Vol. 26 (2), pp. 293-301. Date of Electronic Publication: 2022 Jan 19. |
نوع المنشور: | Meta-Analysis; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9815755 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5608 (Electronic) Linking ISSN: 13657852 NLM ISO Abbreviation: Prostate Cancer Prostatic Dis Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2002->: London : Nature Publishing Group Original Publication: Houndmills, Basingstoke, UK : Stockton Press, c1997- |
مواضيع طبية MeSH: | Androgens*/genetics , Androgens*/metabolism , Prostatic Neoplasms, Castration-Resistant*/drug therapy , Prostatic Neoplasms, Castration-Resistant*/genetics , Prostatic Neoplasms, Castration-Resistant*/metabolism, Male ; Humans ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Glucocorticoids/pharmacology ; Ligands ; Testosterone/metabolism ; Steroids/metabolism ; Mutation ; Prednisolone/pharmacology ; Dexamethasone/pharmacology |
مستخلص: | Background: Androgen receptor (AR) ligand-binding domain (LBD) mutations occur in ~20% of all castration-resistant prostate cancer (CRPC) patients. These mutations confer ligand promiscuity, but the affinity for many steroid hormone pathway intermediates is unknown. In this study, we investigated the stimulation of clinically relevant AR-LBD mutants by endogenous and exogenous steroid hormones present in CRPC patients to unravel their potential contribution to AR pathway reactivation. Methods: A meta-analysis of studies reporting untargeted analysis of AR mutants was performed to identify clinically relevant AR-LBD mutations. Using luciferase reporter and quantitative fluorescent microscopy, these AR mutants were screened for sensitivity for various endogenous steroids and synthetic glucocorticoids used in the treatment of CRPC. Results: The meta-analysis revealed that AR Conclusion: Both testosterone and 11KT effectively contribute to AR (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.) |
References: | Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10:33–9. (PMID: 1470263210.1038/nm972) Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10:440–8. (PMID: 1476006310.1158/1078-0432.CCR-1146-03) Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815–25. (PMID: 1651060410.1158/0008-5472.CAN-05-4000) Beltran H, Yelensky R, Frampton GM, Park K, Downing SR, MacDonald TY, et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013;63:920–6. (PMID: 2298167510.1016/j.eururo.2012.08.053) Jernberg E, Bergh A, Wikstrom P. Clinical relevance of androgen receptor alterations in prostate cancer. Endocr Connect. 2017;6:R146–R61. (PMID: 29030409564057410.1530/EC-17-0118) Zhao XY, Boyle B, Krishnan AV, Navone NM, Peehl DM, Feldman D. Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a. J Urol. 1999;162:2192–9. (PMID: 1056961810.1016/S0022-5347(05)68158-X) Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, et al. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med. 2000;6:703–6. (PMID: 1083569010.1038/76287) van de Wijngaart DJ, Molier M, Lusher SJ, Hersmus R, Jenster G, Trapman J, et al. Systematic structure-function analysis of androgen receptor Leu701 mutants explains the properties of the prostate cancer mutant L701H. J Biol Chem. 2010;285:5097–105. (PMID: 2000769310.1074/jbc.M109.039958) Lallous N, Volik SV, Awrey S, Leblanc E, Tse R, Murillo J, et al. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol. 2016;17:10. (PMID: 26813233472913710.1186/s13059-015-0864-1) Prekovic S, van Royen ME, Voet AR, Geverts B, Houtman R, Melchers D, et al. The effect of F877L and T878A mutations on androgen receptor response to enzalutamide. Mol Cancer Ther. 2016;15:1702–12. (PMID: 2719675610.1158/1535-7163.MCT-15-0892) Pretorius E, Africander DJ, Vlok M, Perkins MS, Quanson J, Storbeck KH. 11-ketotestosterone and 11-ketodihydrotestosterone in castration resistant prostate cancer: potent androgens which can no longer be ignored. PLoS One. 2016;11:e0159867. (PMID: 27442248495629910.1371/journal.pone.0159867) Storbeck KH, Bloem LM, Africander D, Schloms L, Swart P, Swart AC. 11beta-Hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19 steroids with androgenic activity: a putative role in castration resistant prostate cancer? Mol Cell Endocrinol. 2013;377:135–46. (PMID: 2385600510.1016/j.mce.2013.07.006) Rege J, Nakamura Y, Satoh F, Morimoto R, Kennedy MR, Layman LC, et al. Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein 19-carbon steroids before and after ACTH stimulation. J Clin Endocrinol Metab. 2013;98:1182–8. (PMID: 23386646359047310.1210/jc.2012-2912) Snaterse G, van Dessel LF, van Riet J, Taylor AE, van der Vlugt-Daane M, Hamberg P, et al. 11-Ketotestosterone is the predominant active androgen in prostate cancer patients after castration. JCI Insight. 2021;6.e148507. (PMID: 339745608262344) Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A, et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol. 2017;28:1508–16. (PMID: 28472366583404310.1093/annonc/mdx155) Marques RB, van Weerden WM, Erkens-Schulze S, de Ridder CM, Bangma CH, Trapman J, et al. The human PC346 xenograft and cell line panel: a model system for prostate cancer progression. Eur Urol. 2006;49:245–57. (PMID: 1641366410.1016/j.eururo.2005.12.035) Farla P, Hersmus R, Geverts B, Mari PO, Nigg AL, Dubbink HJ, et al. The androgen receptor ligand-binding domain stabilizes DNA binding in living cells. J Struct Biol. 2004;147:50–61. (PMID: 1510960510.1016/j.jsb.2004.01.002) Farla P, Hersmus R, Trapman J, Houtsmuller AB. Antiandrogens prevent stable DNA-binding of the androgen receptor. J Cell Sci. 2005;118:4187–98. (PMID: 1614123210.1242/jcs.02546) Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, O’Malley BW. Steroid receptor induction of gene transcription: a two-step model. Proc Natl Acad Sci USA. 1997;94:7879–84. (PMID: 92232812152310.1073/pnas.94.15.7879) van Royen ME, van de Wijngaart DJ, Cunha SM, Trapman J, Houtsmuller AB. A multi-parameter imaging assay identifies different stages of ligand-induced androgen receptor activation. Cytom A 2013;83:806–17. (PMID: 10.1002/cyto.a.22284) Moll JM, Kumagai J, van Royen ME, Teubel WJ, van Soest RJ, French PJ, et al. A bypass mechanism of abiraterone-resistant prostate cancer: Accumulating CYP17A1 substrates activate androgen receptor signaling. Prostate 2019;79:937–48. (PMID: 31017696659347010.1002/pros.23799) Romijn JC, Verkoelen CF, Schroeder FH. Application of the MTT assay to human prostate cancer cell lines in vitro: establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects. Prostate 1988;12:99–110. (PMID: 312649310.1002/pros.2990120112) Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl J Med. 2013;368:138–48. (PMID: 2322817210.1056/NEJMoa1209096) de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. (PMID: 21612468347114910.1056/NEJMoa1014618) Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97. (PMID: 2289455310.1056/NEJMoa1207506) Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33. (PMID: 24881730441893110.1056/NEJMoa1405095) Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, et al. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun. 1990;173:534–40. (PMID: 226096610.1016/S0006-291X(05)80067-1) Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y. et al. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA. 2001;98:4904–9. (PMID: 113202413313610.1073/pnas.081565498) Duff J, McEwan IJ. Mutation of histidine 874 in the androgen receptor ligand-binding domain leads to promiscuous ligand activation and altered p160 coactivator interactions. Mol Endocrinol. 2005;19:2943–54. (PMID: 1608151710.1210/me.2005-0231) Matias PM, Donner P, Coelho R, Thomaz M, Peixoto C, Macedo S, et al. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J Biol Chem. 2000;275:26164–71. (PMID: 1084004310.1074/jbc.M004571200) Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EM. Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J Biol Chem. 2007;282:25801–16. (PMID: 1759176710.1074/jbc.M703268200) Brooke GN, Parker MG, Bevan CL. Mechanisms of androgen receptor activation in advanced prostate cancer: differential co-activator recruitment and gene expression. Oncogene. 2008;27:2941–50. (PMID: 1803795610.1038/sj.onc.1210955) Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, et al. Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res. 2015;21:2315–24. (PMID: 2571268310.1158/1078-0432.CCR-14-2666) Wright C, O’Day P, Alyamani M, Sharifi N, Auchus RJ. Abiraterone acetate treatment lowers 11-oxygenated androgens. Eur J Endocrinol. 2020;182:413–21. (PMID: 32045360709606010.1530/EJE-19-0905) Romanel A, Gasi Tandefelt D, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, et al. Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med. 2015;7:312re10. (PMID: 26537258611241010.1126/scitranslmed.aac9511) Chen EJ, Sowalsky AG, Gao S, Cai C, Voznesensky O, Schaefer R, et al. Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res. 2015;21:1273–80. (PMID: 2532035810.1158/1078-0432.CCR-14-1220) Attard G, Merseburger AS, Arlt W, Sternberg CN, Feyerabend S, Berruti A, et al. Assessment of the safety of glucocorticoid regimens in combination with abiraterone acetate: a randomized, open-label phase 2 study. JAMA Oncol. 2019;5:1159–67. (PMID: 31246234660409210.1001/jamaoncol.2019.1011) Carreira S, Romanel A, Goodall J, Grist E, Ferraldeschi R, Miranda S, et al. Tumor clone dynamics in lethal prostate cancer. Sci Transl Med. 2014;6:254ra125. (PMID: 25232177442217810.1126/scitranslmed.3009448) Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012;72:2176–82. (PMID: 22411952428170810.1158/0008-5472.CAN-11-3980) Li J, Alyamani M, Zhang A, Chang KH, Berk M, Li Z, et al. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer. Elife. 2017;6.e20183. Krishnan AV, Zhao XY, Swami S, Brive L, Peehl DM, Ely KR, et al. A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer. Endocrinology 2002;143:1889–900. (PMID: 1195617210.1210/endo.143.5.8778) Lorente D, Omlin A, Ferraldeschi R, Pezaro C, Perez R, Mateo J, et al. Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone. Br J Cancer. 2014;111:2248–53. (PMID: 25314055426444310.1038/bjc.2014.531) Wyatt AW, Azad AA, Volik SV, Annala M, Beja K, McConeghy B, et al. Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer. JAMA Oncol. 2016;2:1598–606. (PMID: 27148695509769010.1001/jamaoncol.2016.0494) Claps M, Petrelli F, Caffo O, Amoroso V, Roca E, Mosca A, et al. Testosterone Levels and Prostate Cancer Prognosis: Systematic Review and Meta-analysis. Clin Genitourin Cancer. 2018;16:165–75 e2. (PMID: 2945463810.1016/j.clgc.2018.01.005) Miura N, Mori K, Mostafaei H, Quhal F, Sari Motlagh R, Abufaraj M, et al. Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis. Int J Clin Oncol. 2020;25:1881–91. (PMID: 32681382757235010.1007/s10147-020-01747-1) Ueland GA, Methlie P, Kellmann R, Bjorgaas M, Asvold BO, Thorstensen K, et al. Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test. Eur J Endocrinol. 2017;176:705–13. (PMID: 2829835310.1530/EJE-17-0078) Snaterse G, Visser JA, Arlt W, Hofland J. Circulating steroid hormone variations throughout different stages of prostate cancer. Endocr Relat Cancer. 2017;24:R403–R20. (PMID: 2892406410.1530/ERC-17-0155) |
المشرفين على المادة: | 0 (Androgens) 0 (Receptors, Androgen) 0 (Glucocorticoids) 0 (Ligands) 3XMK78S47O (Testosterone) 0 (Steroids) 9PHQ9Y1OLM (Prednisolone) 7S5I7G3JQL (Dexamethasone) |
تواريخ الأحداث: | Date Created: 20220120 Date Completed: 20230609 Latest Revision: 20230614 |
رمز التحديث: | 20230615 |
DOI: | 10.1038/s41391-022-00491-z |
PMID: | 35046557 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-5608 |
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DOI: | 10.1038/s41391-022-00491-z |