Portal de Periódicos da CAPES

TWO MUTATIONS IDENTIFIED IN THE ANDROGEN RECEPTOR OF THE NEW HUMAN PROSTATE CANCER CELL LINE MDA PCA 2A

1999; Lippincott Williams & Wilkins; Volume: 162; Issue: 6 Linguagem: Inglês

10.1016/s0022-5347(05)68158-x

1527-3792

Xiao-Yan Zhao, Bryan Boyle, Aruna V. Krishnan, Nora M. Navone, Donna M. Peehl, David Feldman,

Ubiquitin and proteasome pathways

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Dec 1999TWO MUTATIONS IDENTIFIED IN THE ANDROGEN RECEPTOR OF THE NEW HUMAN PROSTATE CANCER CELL LINE MDA PCA 2A XIAO-YAN ZHAO, BRYAN BOYLE, ARUNA V. KRISHNAN, NORA M. NAVONE, DONNA M. PEEHL, and DAVID FELDMAN XIAO-YAN ZHAOXIAO-YAN ZHAO , BRYAN BOYLEBRYAN BOYLE , ARUNA V. KRISHNANARUNA V. KRISHNAN , NORA M. NAVONENORA M. NAVONE , DONNA M. PEEHLDONNA M. PEEHL , and DAVID FELDMANDAVID FELDMAN View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)68158-XAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We have characterized the androgen receptor (AR) in a new human prostate cancer cell line, MDA PCa 2a, that has recently been established from a bone metastasis of a patient whose cancer exhibited androgen-independent growth. Materials and Methods: Androgen responsiveness of these cells was assessed by measuring the effect of DHT and R1881 on cell growth and PSA secretion. Scatchard analysis was used to characterize the affinity and abundance of AR protein. Using a PCR based strategy, genomic DNA of the entire coding region of AR gene was sequenced to identify possible mutations. Results: These cells express abundant AR (Nmax = 685 ± 149 fmol./mg. protein), but the AR binding affinity (Kd) for DHT is only 25 nM, ∼50-fold lower affinity than the mutated AR in LNCaP prostate cancer cells (Kd = 0.5 nM) or the wildtype AR in MCF-7 breast cancer cells (Kd = 0.4 nM). Two mutations, L701H and T877A, were identified in the ligand binding domain of the AR gene. Compared with LNCaP cells, the new cell line is significantly less responsive to DHT and R1881 as well as to other androgens such as testosterone, androstenedione, and DHEA. Similar to LNCaP cells, the ligand specificity of the AR in MDA PCa 2a cells appears to be relaxed and non-androgens such as progesterone and estradiol act as agonists although with less potency than in LNCaP cells. Interestingly, in the absence of androgens, the new cell line expresses 15-fold higher baseline levels of PSA than LNCaP. Conclusions: Two mutations were identified in the AR gene of the MDA PCa 2a cell line that are likely responsible for the decreased androgen sensitivity and altered ligand specificity observed in these cells. Thus, this new cell line with partial androgen responsiveness and PSA expression can serve as a functionally relevant model system of bone metastatic prostate cancer, and can be used to investigate the role of AR mutations in prostate cancer and its progression to androgen independence. References 1 : Current concepts in the treatment of cancer of the prostate. In: . Boston: Birkhauser1996: 379. Google Scholar 2 : Androgen receptor mutations in prostate cancer. Mt. Sinai. J. Med.1996; 63: 403. Medline, Google Scholar 3 : Target to apoptosis: a hopeful weapon for prostate cancer. Prostate1997; 32: 284. Crossref, Medline, Google Scholar 4 : The androgen receptor gene mutations database. Nucleic Acids Res.1998; 26: 234. Crossref, Medline, Google Scholar 5 : Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: high affinity for progestagenic and estrogenic steroids. Biochim. Biophys. Acta1990; 1052: 187. Crossref, Medline, Google Scholar 6 : Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res.1994; 54: 2861. Medline, Google Scholar 7 : Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clin. Cancer Res.1997; 3: 2493. Medline, Google Scholar 8 : 1α,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent. Endocrinol.1997; 138: 3290. Crossref, Medline, Google Scholar 9 : A study of conditions and mechanisms of the diphenyl amine colorimetric estimation of deoxyribonucleic acid. Biochem. J.1956; 62: 315. Crossref, Medline, Google Scholar 10 : A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal. Biochem.1976; 72: 248. Crossref, Medline, Google Scholar 11 : Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc. Natl. Acad. Sci. USA1989; 86: 9534. Crossref, Medline, Google Scholar 12 : LNCaP model of human prostatic carcinoma. Cancer Res.1983; 43: 1809. Medline, Google Scholar 13 : Comparative studies of 5 alpha-reductase inhibitors within MCF-7 human breast cancer cells. J. Steroid Biochem.1984; 20: 1095. Crossref, Medline, Google Scholar 14 : A canonical structure for the ligand-binding domain of nuclear receptors [see comments] [published erratum appears in Nat. Struct. Biol.1996; 3: 206. Google Scholar 15 : Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr. Rev.1995; 16: 271. [published erratum appears in Endocr. Rev., 16: 546, 1995]. Medline, Google Scholar 16 : Androgen receptor gene mutations in human prostate cancer. J. Steroid Biochem. Mol. Biol.1993; 46: 759. Crossref, Medline, Google Scholar 17 : Androgen resistance due to mutation of the androgen receptor. Clin. Invest. Med.1992; 15: 456. Medline, Google Scholar 18 : In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat. Genet.1995; 9: 401. Crossref, Medline, Google Scholar 19 : Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res.1997; 57: 314. Medline, Google Scholar From the Departments of Medicine and Urology, Stanford University School of Medicine, Stanford, California and the Department of GU Medical Oncology, M. D. Anderson Cancer Center, Houston, Texas© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited by Shiota M, Akamatsu S, Tsukahara S, Nagakawa S, Matsumoto T and Eto M Androgen receptor mutations for precision medicine in prostate cancerEndocrine-Related Cancer, 10.1530/ERC-22-0140, VOL. 29, NO. 10, (R143-R155) Yu E and Aragon-Ching J (2022) Advances with androgen deprivation therapy for prostate cancerExpert Opinion on Pharmacotherapy, 10.1080/14656566.2022.2033210, VOL. 23, NO. 9, (1015-1033), Online publication date: 13-Jun-2022. Li X, Li M, Huang M, Lin Q, Fang Q, Liu J, Chen X, Liu L, Zhan X, Shan H, Lu D, Li Q, Li Z and Zhu X (2022) The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicineBiomedicine & Pharmacotherapy, 10.1016/j.biopha.2022.113064, VOL. 150, (113064), Online publication date: 1-Jun-2022. Chai X, Sun H, Zhou W, Chen C, Shan L, Yang Y, He J, Pang J, Yang L, Wang X, Cui S, Fu Y, Xu X, Xu L, Yao X, Li D and Hou T (2022) Discovery of N -(4-(Benzyloxy)-phenyl)-sulfonamide Derivatives as Novel Antagonists of the Human Androgen Receptor Targeting the Activation Function 2 Journal of Medicinal Chemistry, 10.1021/acs.jmedchem.1c01938, VOL. 65, NO. 3, (2507-2521), Online publication date: 10-Feb-2022. Snaterse G, Mies R, van Weerden W, French P, Jonker J, Houtsmuller A, van Royen M, Visser J and Hofland J (2022) Androgen receptor mutations modulate activation by 11-oxygenated androgens and glucocorticoidsProstate Cancer and Prostatic Diseases, 10.1038/s41391-022-00491-z de Bono J, Guo C, Gurel B, De Marzo A, Sfanos K, Mani R, Gil J, Drake C and Alimonti A (2020) Prostate carcinogenesis: inflammatory stormsNature Reviews Cancer, 10.1038/s41568-020-0267-9, VOL. 20, NO. 8, (455-469), Online publication date: 1-Aug-2020. Elbadawy M, Abugomaa A, Yamawaki H, Usui T and Sasaki K (2020) Development of Prostate Cancer Organoid Culture Models in Basic Medicine and Translational ResearchCancers, 10.3390/cancers12040777, VOL. 12, NO. 4, (777) Badal S, Campbell K, Valentine H and Ragin C (2019) The need for cell lines from diverse ethnic backgrounds for prostate cancer researchNature Reviews Urology, 10.1038/s41585-019-0234-y, VOL. 16, NO. 12, (691-692), Online publication date: 1-Dec-2019. Vaddi P, Stamnes M, Cao H and Chen S (2019) Elimination of SOX2/OCT4-Associated Prostate Cancer Stem Cells Blocks Tumor Development and Enhances Therapeutic ResponseCancers, 10.3390/cancers11091331, VOL. 11, NO. 9, (1331) Namekawa T, Ikeda K, Horie-Inoue K and Inoue S (2019) Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived CellsCells, 10.3390/cells8010074, VOL. 8, NO. 1, (74) Faivre E, Wilcox D, Lin X, Hessler P, Torrent M, He W, Uziel T, Albert D, McDaniel K, Kati W and Shen Y (2017) Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075Molecular Cancer Research, 10.1158/1541-7786.MCR-16-0221, VOL. 15, NO. 1, (35-44), Online publication date: 1-Jan-2017. Wadosky K and Koochekpour S (2016) Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancerOncotarget, 10.18632/oncotarget.10901, VOL. 7, NO. 39, (64447-64470), Online publication date: 27-Sep-2016. Swami S, Krishnan A, Williams J, Aggarwal A, Albertelli M, Horst R, Feldman B and Feldman D Vitamin D mitigates the adverse effects of obesity on breast cancer in miceEndocrine-Related Cancer, 10.1530/ERC-15-0557, VOL. 23, NO. 4, (251-264) Watson P, Arora V and Sawyers C (2015) Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancerNature Reviews Cancer, 10.1038/nrc4016, VOL. 15, NO. 12, (701-711), Online publication date: 1-Dec-2015. Lucarelli G, Rutigliano M, Galleggiante V, Giglio A, Palazzo S, Ferro M, Simone C, Bettocchi C, Battaglia M and Ditonno P (2015) Metabolomic profiling for the identification of novel diagnostic markers in prostate cancerExpert Review of Molecular Diagnostics, 10.1586/14737159.2015.1069711, VOL. 15, NO. 9, (1211-1224), Online publication date: 2-Sep-2015. Zaman N, Giannopoulos P, Chowdhury S, Bonneil E, Thibault P, Wang E, Trifiro M, Paliouras M and Saleem M (2014) Proteomic-Coupled-Network Analysis of T877A-Androgen Receptor Interactomes Can Predict Clinical Prostate Cancer Outcomes between White (Non-Hispanic) and African-American GroupsPLoS ONE, 10.1371/journal.pone.0113190, VOL. 9, NO. 11, (e113190) Culig Z and Santer F (2014) Androgen receptor signaling in prostate cancerCancer and Metastasis Reviews, 10.1007/s10555-013-9474-0, VOL. 33, NO. 2-3, (413-427), Online publication date: 1-Sep-2014. Simmons J, Elshafae S, Keller E, McCauley L and Rosol T (2014) Review of Animal Models of Prostate Cancer Bone MetastasisVeterinary Sciences, 10.3390/vetsci1010016, VOL. 1, NO. 1, (16-39) van Royen M, van de Wijngaart D, Cunha S, Trapman J and Houtsmuller A (2013) A multi-parameter imaging assay identifies different stages of ligand-induced androgen receptor activationCytometry Part A, 10.1002/cyto.a.22284, VOL. 83, NO. 9, (806-817), Online publication date: 1-Sep-2013. Wu X, Gong S, Roy-Burman P, Lee P and Culig Z Current mouse and cell models in prostate cancer researchEndocrine-Related Cancer, 10.1530/ERC-12-0285, VOL. 20, NO. 4, (R155-R170) Sampson N, Neuwirt H, Puhr M, Klocker H and Eder I In vitro model systems to study androgen receptor signaling in prostate cancerEndocrine-Related Cancer, 10.1530/ERC-12-0401, VOL. 20, NO. 2, (R49-R64) Waltering K, Urbanucci A and Visakorpi T (2012) Androgen receptor (AR) aberrations in castration-resistant prostate cancerMolecular and Cellular Endocrinology, 10.1016/j.mce.2011.12.019, VOL. 360, NO. 1-2, (38-43), Online publication date: 1-Sep-2012. Thompson V, Day T, Bianco-Miotto T, Selth L, Han G, Thomas M, Buchanan G, Scher H, Nelson C, Greenberg N, Butler L and Tilley W (2012) A gene signature identified using a mouse model of androgen receptor-dependent prostate cancer predicts biochemical relapse in human diseaseInternational Journal of Cancer, 10.1002/ijc.26414, VOL. 131, NO. 3, (662-672), Online publication date: 1-Aug-2012. Andrieu T, Bertolini R, Nichols S, Setoud R, Frey F, Baker M and Frey B (2011) A novel steroidal antiandrogen targeting wild type and mutant androgen receptorsBiochemical Pharmacology, 10.1016/j.bcp.2011.08.020, VOL. 82, NO. 11, (1651-1662), Online publication date: 1-Dec-2011. Krishnan A and Feldman D (2011) Vitamin D and Prostate Cancer Vitamin D, 10.1016/B978-0-12-381978-9.10086-1, (1675-1709), . Koochekpour S (2010) Androgen receptor signaling and mutations in prostate cancerAsian Journal of Andrology, 10.1038/aja.2010.89, VOL. 12, NO. 5, (639-657), Online publication date: 1-Sep-2010. van de Wijngaart D, Molier M, Lusher S, Hersmus R, Jenster G, Trapman J and Dubbink H (2010) Systematic Structure-Function Analysis of Androgen Receptor Leu701 Mutants Explains the Properties of the Prostate Cancer Mutant L701HJournal of Biological Chemistry, 10.1074/jbc.M109.039958, VOL. 285, NO. 7, (5097-5105), Online publication date: 1-Feb-2010. Febbo P and Kantoff P (2010) Genomic Evaluation and Management of Prostate Cancer Essentials of Genomic and Personalized Medicine, 10.1016/B978-0-12-374934-5.00037-4, (477-492), . Malinowska K, Cavarretta I, Susani M, Wrulich O, Überall F, Kenner L and Culig Z (2009) Identification of µ-crystallin as an androgen-regulated gene in human prostate cancerThe Prostate, 10.1002/pros.20956, VOL. 69, NO. 10, (1109-1118), Online publication date: 1-Jul-2009. Bergerat J and Céraline J (2008) Pleiotropic functional properties of androgen receptor mutants in prostate cancerHuman Mutation, 10.1002/humu.20848, VOL. 30, NO. 2, (145-157), Online publication date: 1-Feb-2009. Febbo P and Kantoff P (2009) Prostate Cancer Genomic and Personalized Medicine, 10.1016/B978-0-12-369420-1.00074-3, (898-912), . Watson P and Sawyers C (2009) Molecular Biology of Novel Targets Identified Through Study of Castration-Recurrent Prostate Cancer Androgen Action in Prostate Cancer, 10.1007/978-0-387-69179-4_32, (743-754), . Dagvadorj A, Tan S, Liao Z, Cavalli L, Haddad B and Nevalainen M (2008) Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 TumorClinical Cancer Research, 10.1158/1078-0432.CCR-08-0979, VOL. 14, NO. 19, (6062-6072), Online publication date: 1-Oct-2008. Shah S, Hess-Wilson J, Webb S, Daly H, Godoy-Tundidor S, Kim J, Boldison J, Daaka Y and Knudsen K (2008) 2,2-Bis(4-Chlorophenyl)-1,1-Dichloroethylene Stimulates Androgen Independence in Prostate Cancer Cells through Combinatorial Activation of Mutant Androgen Receptor and Mitogen-Activated Protein Kinase PathwaysMolecular Cancer Research, 10.1158/1541-7786.MCR-07-2166, VOL. 6, NO. 9, (1507-1520), Online publication date: 1-Sep-2008. Helenius M, Waltering K and Visakorpi T (2008) Somatic Genetic Changes in Prostate Cancer Prostate Cancer, 10.1007/978-1-60327-079-3_5, (99-128), . Arnold J, Liu X, Allen J, Le H, McFann K and Blackman M (2007) Androgen receptor or estrogen receptor-β blockade alters DHEA-, DHT-, and E2-induced proliferation and PSA production in human prostate cancer cellsThe Prostate, 10.1002/pros.20585, VOL. 67, NO. 11, (1152-1162), Online publication date: 1-Aug-2007. Liu X, Kirschenbaum A, Yao S, Liu G, Aaronson S and Levine A (2007) Androgen-Induced Wnt Signaling in Preosteoblasts Promotes the Growth of MDA-PCa-2b Human Prostate Cancer CellsCancer Research, 10.1158/0008-5472.CAN-07-0478, VOL. 67, NO. 12, (5747-5753), Online publication date: 15-Jun-2007. Robzyk K, Oen H, Buchanan G, Butler L, Tilley W, Mandal A, Rosen N and Caplan A (2007) Uncoupling of hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptorMolecular and Cellular Endocrinology, 10.1016/j.mce.2007.01.016, VOL. 268, NO. 1-2, (67-74), Online publication date: 1-Mar-2007. Klocker H, Eder I, Comuzzi B, Bartsch G and Culig Z Androgen Receptor Function in Prostate Cancer Progression Prostate Cancer, 10.1007/978-1-59745-224-3_6, (87-105) Heemers H, Verhoeven G and Swinnen J (2006) Androgen Activation of the Sterol Regulatory Element-Binding Protein Pathway: Current InsightsMolecular Endocrinology, 10.1210/me.2005-0479, VOL. 20, NO. 10, (2265-2277), Online publication date: 1-Oct-2006. Yuan X, Li T, Wang H, Zhang T, Barua M, Borgesi R, Bubley G, Lu M and Balk S (2006) Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer CellsThe American Journal of Pathology, 10.2353/ajpath.2006.051047, VOL. 169, NO. 2, (682-696), Online publication date: 1-Aug-2006. Balakumaran B and Febbo P (2006) New Insights into Prostate Cancer BiologyHematology/Oncology Clinics of North America, 10.1016/j.hoc.2006.06.005, VOL. 20, NO. 4, (773-796), Online publication date: 1-Aug-2006. Butler L, Centenera M, Neufing P, Buchanan G, Choong C, Ricciardelli C, Saint K, Lee M, Ochnik A, Yang M, Brown M and Tilley W (2006) Suppression of Androgen Receptor Signaling in Prostate Cancer Cells by an Inhibitory Receptor VariantMolecular Endocrinology, 10.1210/me.2004-0401, VOL. 20, NO. 5, (1009-1024), Online publication date: 1-May-2006. Le H, Arnold J, McFann K and Blackman M (2006) DHT and testosterone, but not DHEA or E 2 , differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells American Journal of Physiology-Endocrinology and Metabolism, 10.1152/ajpendo.00451.2005, VOL. 290, NO. 5, (E952-E960), Online publication date: 1-May-2006. Srinivas S, Krishnan A, Colocci N and Feldman D (2006) Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancerUrology, 10.1016/j.urology.2005.11.004, VOL. 67, NO. 5, (1001-1006), Online publication date: 1-May-2006. Murthy S, Agoulnik I and Weigel N (2005) Androgen receptor signaling and vitamin D receptor action in prostate cancer cellsThe Prostate, 10.1002/pros.20251, VOL. 64, NO. 4, (362-372), Online publication date: 1-Sep-2005. Marquis J, Hillier S, Dinaut A, Rodrigues D, Mitra K, Essigmann J and Croy R (2005) Disruption of Gene Expression and Induction of Apoptosis in Prostate Cancer Cells by a DNA-Damaging Agent Tethered to an Androgen Receptor LigandChemistry & Biology, 10.1016/j.chembiol.2005.05.009, VOL. 12, NO. 7, (779-787), Online publication date: 1-Jul-2005. Arnold J, Le H, McFann K and Blackman M (2005) Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cellsAmerican Journal of Physiology-Endocrinology and Metabolism, 10.1152/ajpendo.00454.2004, VOL. 288, NO. 3, (E573-E584), Online publication date: 1-Mar-2005. SOBEL R and SADAR M (2018) CELL LINES USED IN PROSTATE CANCER RESEARCH: A COMPENDIUM OF OLD AND NEW LINES—PART 1Journal of Urology, VOL. 173, NO. 2, (342-359), Online publication date: 1-Feb-2005. Han G, Buchanan G, Ittmann M, Harris J, Yu X, DeMayo F, Tilley W and Greenberg N (2005) Mutation of the androgen receptor causes oncogenic transformation of the prostateProceedings of the National Academy of Sciences, 10.1073/pnas.0408925102, VOL. 102, NO. 4, (1151-1156), Online publication date: 25-Jan-2005. Wetherill Y, Fisher N, Staubach A, Danielsen M, de Vere White R and Knudsen K (2005) Xenoestrogen Action in Prostate Cancer: Pleiotropic Effects Dependent on Androgen Receptor StatusCancer Research, 10.1158/0008-5472.54.65.1, VOL. 65, NO. 1, (54-65), Online publication date: 1-Jan-2005. Céraline J, Cruchant M, Erdmann E, Erbs P, Kurtz J, Duclos B, Jacqmin D, Chopin D, Dufour P and Bergerat J Constitutively Active Androgen Receptor Variant Detected in a Human Prostate Cancer Hormonal Carcinogenesis IV, 10.1007/0-387-23761-5_31, (336-342) Linja M and Visakorpi T (2004) Alterations of androgen receptor in prostate cancerThe Journal of Steroid Biochemistry and Molecular Biology, 10.1016/j.jsbmb.2004.10.012, VOL. 92, NO. 4, (255-264), Online publication date: 1-Nov-2004. Novelli G, Margiotti K, Chiocca A, Spera E, Micali F and Reichardt J (2004) Pharmacogenetics of human androgens and prostate cancer – an updatePharmacogenomics, 10.1517/phgs.5.3.283.29828, VOL. 5, NO. 3, (283-294), Online publication date: 1-Apr-2004. Céraline J, Cruchant M, Erdmann E, Erbs P, Kurtz J, Duclos B, Jacqmin D, Chopin D and Bergerat J (2003) Constitutive activation of the androgen receptor by a point mutation in the hinge region: A new mechanism for androgen-independent growth in prostate cancerInternational Journal of Cancer, 10.1002/ijc.11404, VOL. 108, NO. 1, (152-157), Online publication date: 1-Jan-2004. van Bokhoven A, Varella-Garcia M, Korch C, Johannes W, Smith E, Miller H, Nordeen S, Miller G and Lucia M (2003) Molecular characterization of human prostate carcinoma cell linesThe Prostate, 10.1002/pros.10290, VOL. 57, NO. 3, (205-225), Online publication date: 1-Nov-2003. CULIG Z, KLOCKER H, BARTSCH G, STEINER H and HOBISCH A (2018) Androgen Receptors in Prostate CancerJournal of Urology, VOL. 170, NO. 4 Part 1, (1363-1369), Online publication date: 1-Oct-2003. Peehl D, Krishnan A and Feldman D (2003) Pathways Mediating the Growth-Inhibitory Actions of Vitamin D in Prostate CancerThe Journal of Nutrition, 10.1093/jn/133.7.2461S, VOL. 133, NO. 7, (S2461-S2469), Online publication date: 1-Jul-2003. Comuzzi B, Lambrinidis L, Rogatsch H, Godoy-Tundidor S, Knezevic N, Krhen I, Marekovic Z, Bartsch G, Klocker H, Hobisch A and Culig Z (2003) The Transcriptional Co-Activator cAMP Response Element-Binding Protein-Binding Protein Is Expressed in Prostate Cancer and Enhances Androgen- and Anti-Androgen-Induced Androgen Receptor FunctionThe American Journal of Pathology, 10.1016/S0002-9440(10)63814-X, VOL. 162, NO. 1, (233-241), Online publication date: 1-Jan-2003. Marcelli M, Lamb D, Weigel N and Cunningham G (2003) Androgen Signaling in Prostatic Neoplasia and Hyperplasia Androgens in Health and Disease, 10.1007/978-1-59259-388-0_9, (157-189), . Balk S (2002) Androgen receptor as a target in androgen-independent prostate cancerUrology, 10.1016/S0090-4295(02)01593-5, VOL. 60, NO. 3, (132-138), Online publication date: 1-Sep-2002. Steketee K, Timmerman L, Ziel-van der Made A, Doesburg P, Brinkmann A and Trapman J (2002) Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancerInternational Journal of Cancer, 10.1002/ijc.10495, VOL. 100, NO. 3, (309-317), Online publication date: 20-Jul-2002. Gelmann E (2002) Molecular Biology of the Androgen ReceptorJournal of Clinical Oncology, 10.1200/JCO.2002.10.018, VOL. 20, NO. 13, (3001-3015), Online publication date: 1-Jul-2002. González-Espinosa D, Jiménez Ríos M and Gutiérrez-López A (2002) Aspectos clínicos de la biología molecular del cáncer de próstataClinical aspects of the molecular biology of prostate cancerRevista de Oncología, 10.1007/BF02732508, VOL. 4, NO. 5, (241-249), Online publication date: 1-Jun-2002. Vidanes G, Paton V, Wallen E, Peehl D, Navone N and Brooks J (2002) Silencing of ?-class glutathione S-transferase in MDA PCa 2a and MDA PCa 2b cellsThe Prostate, 10.1002/pros.10093, VOL. 51, NO. 4, (225-230), Online publication date: 1-Jun-2002. Krishnan A, Zhao X, Swami S, Brive L, Peehl D, Ely K and Feldman D (2002) A Glucocorticoid-Responsive Mutant Androgen Receptor Exhibits Unique Ligand Specificity: Therapeutic Implications for Androgen-Independent Prostate CancerEndocrinology, 10.1210/endo.143.5.8778, VOL. 143, NO. 5, (1889-1900), Online publication date: 1-May-2002. Yang E, Maiorino C, Roos B, Knight S and Burnstein K (2002) Vitamin D-mediated growth inhibition of an androgen-ablated LNCaP cell line model of human prostate cancerMolecular and Cellular Endocrinology, 10.1016/S0303-7207(01)00671-2, VOL. 186, NO. 1, (69-79), Online publication date: 1-Jan-2002. Feldman B and Feldman D (2001) The development of androgen-independent prostate cancerNature Reviews Cancer, 10.1038/35094009, VOL. 1, NO. 1, (34-45), Online publication date: 1-Oct-2001. Han G, Foster B, Mistry S, Buchanan G, Harris J, Tilley W and Greenberg N (2001) Hormone Status Selects for Spontaneous Somatic Androgen Receptor Variants That Demonstrate Specific Ligand and Cofactor Dependent Activities in Autochthonous Prostate CancerJournal of Biological Chemistry, 10.1074/jbc.M008207200, VOL. 276, NO. 14, (11204-11213), Online publication date: 1-Apr-2001. Brive L, Agus D and Ely K (2002) Structure-Based Androgen Receptor Gene Mutation Database: A Tool to Link Molecular Location and Receptor FunctionThe Prostate Journal, 10.1046/j.1525-1411.2001.32004.x, VOL. 3, NO. 2, (76-91) Zhao X and Feldman D (2001) The role of vitamin D in prostate cancerSteroids, 10.1016/S0039-128X(00)00164-1, VOL. 66, NO. 3-5, (293-300), Online publication date: 1-Mar-2001. Novelli G, Margiotti K, Sangiuolo F and Reichardt J (2001) Pharmacogenetics of human androgens and prostatic diseasesPharmacogenomics, 10.1517/14622416.2.1.65, VOL. 2, NO. 1, (65-72), Online publication date: 1-Feb-2001. Culig Z, Klocker H, Bartsch G and Hobisch A (2001) Androgen Receptor Mutations in Carcinoma of the ProstateAmerican Journal of PharmacoGenomics, 10.2165/00129785-200101040-00001, VOL. 1, NO. 4, (241-249), . Culig Z, Hobisch A, Bartsch G and Klocker H (2000) Expression and function of androgen receptor in carcinoma of the prostateMicroscopy Research and Technique, 10.1002/1097-0029(20001201)51:5 3.0.CO;2-M, VOL. 51, NO. 5, (447-455), Online publication date: 1-Dec-2000. Zhao X, Peehl D, Navone N and Feldman D (2000) 1α,25-Dihydroxyvitamin D3 Inhibits Prostate Cancer Cell Growth by Androgen-Dependent and Androgen-Independent Mechanisms*Endocrinology, 10.1210/endo.141.7.7549, VOL. 141, NO. 7, (2548-2556), Online publication date: 1-Jul-2000. (2000) The Prostate Journal DatabaseThe Prostate Journal, 10.1046/j.1525-1411.2000.23007.x, VOL. 2, NO. 3, (168-171), Online publication date: 1-Jul-2000. Zhao X, Malloy P, Krishnan A, Swami S, Navone N, Peehl D and Feldman D (2000) Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptorNature Medicine, 10.1038/76287, VOL. 6, NO. 6, (703-706), Online publication date: 1-Jun-2000. Brinkmann A and Trapman J (2000) Prostate cancer schemes for androgen escapeNature Medicine, 10.1038/76194, VOL. 6, NO. 6, (628-629), Online publication date: 1-Jun-2000. van Weerden W and Romijn J (2000) Use of nude mouse xenograft models in prostate cancer researchThe Prostate, 10.1002/1097-0045(20000601)43:4 3.0.CO;2-I, VOL. 43, NO. 4, (263-271), Online publication date: 1-Jun-2000. Volume 162Issue 6December 1999Page: 2192-2199 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.KeywordsPSAMDA PCa 2aandrogen receptor mutationsLNCaPprostateMetricsAuthor Information XIAO-YAN ZHAO More articles by this author BRYAN BOYLE More articles by this author ARUNA V. KRISHNAN More articles by this author NORA M. NAVONE More articles by this author DONNA M. PEEHL More articles by this author DAVID FELDMAN More articles by this author Expand All Advertisement PDF downloadLoading ...