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HDAC6 Regulation of Androgen Signaling in Prostate Cancer

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Prostate Cancer

Part of the book series: Protein Reviews ((PRON,volume 16))

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Abstract

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and the second leading cause of cancer death in the male population in the USA and other developed nations. Initially, prostate cancer is dependent on androgens for growth, which provides a basis for using androgen deprivation therapy to treat locally advanced or metastatic disease. However, prostate cancer almost always progresses to a castration-resistant phenotype for which few treatment options with improved overall survival are available at present. Multiple studies have shown that active androgen receptor (AR) signaling is still required for development, growth, and progression of castration-resistant prostate cancer (CRPC). Thus, targeting AR signaling, particularly androgen-independent activation of AR signaling, in CRPC may result in novel therapeutic strategies. In this chapter, we summarize recent findings on the regulation of AR signaling by histone deacetylase 6 (HDAC6) and discuss the potential mechanisms by which HDAC6 influences androgen signaling in prostate cancer. We also discuss the potential of targeting HDAC6 in prostate cancer treatment.

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References

  1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O et al (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61:1079–1092

    PubMed  Google Scholar 

  2. Damber JE, Aus G (2008) Prostate cancer. Lancet 371:1710–1721

    PubMed  Google Scholar 

  3. Maluf FC, Smaletz O, Herchenhorn D (2012) Castration-resistant prostate cancer: systemic therapy in 2012. Clinics (Sao Paulo) 67:389–394

    Google Scholar 

  4. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    PubMed  Google Scholar 

  5. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R et al (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10:33–39

    PubMed  Google Scholar 

  6. Huggins C, Hodges CV (1972) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 22:232–240

    PubMed  CAS  Google Scholar 

  7. Shi XB, Ma AH, Tepper CG, Xia L, Gregg JP, Gandour-Edwards R et al (2004) Molecular alterations associated with LNCaP cell progression to androgen independence. Prostate 60:257–271

    PubMed  CAS  Google Scholar 

  8. Zegarra-Moro OL, Schmidt LJ, Huang H, Tindall DJ (2002) Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res 62:1008–1013

    PubMed  CAS  Google Scholar 

  9. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468

    PubMed  CAS  Google Scholar 

  10. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ et al (1996) Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-­resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 14:1756–1764

    PubMed  CAS  Google Scholar 

  11. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512

    PubMed  CAS  Google Scholar 

  12. Diaz M, Patterson SG (2004) Management of androgen-independent prostate cancer. Cancer Control 11:364–373

    PubMed  Google Scholar 

  13. Hellerstedt BA, Pienta KJ (2002) The current state of hormonal therapy for prostate cancer. CA Cancer J Clin 52:154–179

    PubMed  Google Scholar 

  14. Massard C, Fizazi K (2011) Targeting continued androgen receptor signaling in prostate cancer. Clin Cancer Res 17:3876–3883

    PubMed  CAS  Google Scholar 

  15. Labrie F (2004) Adrenal androgens and intracrinology. Semin Reprod Med 22:299–309

    PubMed  CAS  Google Scholar 

  16. Denmeade SR, Lin XS, Isaacs JT (1996) Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer. Prostate 28:251–265

    PubMed  CAS  Google Scholar 

  17. Maitland NJ, Collins AT (2008) Prostate cancer stem cells: a new target for therapy. J Clin Oncol 26:2862–2870

    PubMed  Google Scholar 

  18. Debes JD, Tindall DJ (2004) Mechanisms of androgen-refractory prostate cancer. N Engl J Med 351:1488–1490

    PubMed  CAS  Google Scholar 

  19. Grossmann ME, Huang H, Tindall DJ (2001) Androgen receptor signaling in androgen-­refractory prostate cancer. J Natl Cancer Inst 93:1687–1697

    PubMed  CAS  Google Scholar 

  20. Hara T, Nakamura K, Araki H, Kusaka M, Yamaoka M (2003) Enhanced androgen receptor signaling correlates with the androgen-refractory growth in a newly established MDA PCa 2b-hr human prostate cancer cell subline. Cancer Res 63:5622–5628

    PubMed  CAS  Google Scholar 

  21. Huang ZQ, Li J, Wong J (2002) AR possesses an intrinsic hormone-independent transcriptional activity. Mol Endocrinol 16:924–937

    PubMed  CAS  Google Scholar 

  22. Reddy GP, Barrack ER, Dou QP, Menon M, Pelley R, Sarkar FH et al (2006) Regulatory processes affecting androgen receptor expression, stability, and function: potential targets to treat hormone-refractory prostate cancer. J Cell Biochem 98:1408–1423

    PubMed  CAS  Google Scholar 

  23. Scher HI, Sawyers CL (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol 23:8253–8261

    PubMed  CAS  Google Scholar 

  24. Taplin ME, Balk SP (2004) Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J Cell Biochem 91:483–490

    PubMed  CAS  Google Scholar 

  25. van der Kwast TH, Schalken J, Ruizeveld de Winter JA, van Vroonhoven CC, Mulder E, Boersma W et al (1991) Androgen receptors in endocrine-therapy-resistant human prostate cancer. Int J Cancer 48:189–193

    PubMed  Google Scholar 

  26. Small EJ, Ryan CJ (2006) The case for secondary hormonal therapies in the chemotherapy age. J Urol 176:S66–S71

    PubMed  CAS  Google Scholar 

  27. Gregory CW, Johnson RT Jr, Mohler JL, French FS, Wilson EM (2001) Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res 61:2892–2898

    PubMed  CAS  Google Scholar 

  28. Culig Z, Steiner H, Bartsch G, Hobisch A (2005) Mechanisms of endocrine therapy-­responsive and -unresponsive prostate tumours. Endocr Relat Cancer 12:229–244

    PubMed  CAS  Google Scholar 

  29. Picard D, Yamamoto KR (1987) Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J 6:3333–3340

    PubMed  CAS  Google Scholar 

  30. Pratt WB, Galigniana MD, Morishima Y, Murphy PJ (2004) Role of molecular chaperones in steroid receptor action. Essays Biochem 40:41–58

    PubMed  CAS  Google Scholar 

  31. Veldscholte J, Berrevoets CA, Brinkmann AO, Grootegoed JA, Mulder E (1992) Anti-­androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation. Biochemistry 31:2393–2399

    PubMed  CAS  Google Scholar 

  32. Yeh S, Chang HC, Miyamoto H, Takatera H, Rahman M, Kang HY et al (1999) Differential induction of the androgen receptor transcriptional activity by selective androgen receptor coactivators. Keio J Med 48:87–92

    PubMed  CAS  Google Scholar 

  33. De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL et al (2011) Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proc Natl Acad Sci USA 108:11878–11883

    PubMed  Google Scholar 

  34. Dehm SM, Tindall DJ (2007) Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol Endocrinol 21:2855–2863

    PubMed  CAS  Google Scholar 

  35. Moore TW, Mayne CG, Katzenellenbogen JA (2010) Minireview: Not picking pockets: nuclear receptor alternate-site modulators (NRAMs). Mol Endocrinol 24:683–695

    PubMed  CAS  Google Scholar 

  36. Saporita AJ, Ai J, Wang Z (2007) The Hsp90 inhibitor, 17-AAG, prevents the ­ligand-­independent nuclear localization of androgen receptor in refractory prostate cancer cells. Prostate 67:509–520

    PubMed  CAS  Google Scholar 

  37. Hoimes CJ, Kelly WK (2010) Redefining hormone resistance in prostate cancer. Ther Adv Med Oncol 2:107–123

    PubMed  CAS  Google Scholar 

  38. Kovacs JJ, Cohen TJ, Yao TP (2005) Chaperoning steroid hormone signaling via reversible acetylation. Nucl Recept Signal 3:e004

    PubMed  Google Scholar 

  39. Ni L, Yang CS, Gioeli D, Frierson H, Toft DO, Paschal BM (2010) FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Mol Cell Biol 30:1243–1253

    PubMed  CAS  Google Scholar 

  40. DeFranco DB, Ramakrishnan C, Tang Y (1998) Molecular chaperones and subcellular trafficking of steroid receptors. J Steroid Biochem Mol Biol 65:51–58

    PubMed  CAS  Google Scholar 

  41. Manninen T, Purmonen S, Ylikomi T (2005) Interaction of nuclear receptors with hsp90 in living cells. J Steroid Biochem Mol Biol 96:13–18

    PubMed  CAS  Google Scholar 

  42. Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18:306–360

    PubMed  CAS  Google Scholar 

  43. Finkel T, Duc J, Fearon ER, Dang CV, Tomaselli GF (1993) Detection and modulation in vivo of helix-loop-helix protein-protein interactions. J Biol Chem 268:5–8

    PubMed  CAS  Google Scholar 

  44. Pratt WB (1993) The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 268:21455–21458

    PubMed  CAS  Google Scholar 

  45. Smith DF, Toft DO (1993) Steroid receptors and their associated proteins. Mol Endocrinol 7:4–11

    PubMed  CAS  Google Scholar 

  46. Neckers L (2002) Heat shock protein 90 inhibition by 17-allylamino-17- demethoxygeldanamycin: a novel therapeutic approach for treating hormone-refractory prostate cancer. Clin Cancer Res 8:962–966

    PubMed  CAS  Google Scholar 

  47. Georget V, Terouanne B, Nicolas JC, Sultan C (2002) Mechanism of antiandrogen action: key role of hsp90 in conformational change and transcriptional activity of the androgen receptor. Biochemistry 41:11824–11831

    PubMed  CAS  Google Scholar 

  48. Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW (1994) Derivation of androgen-­independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int J Cancer 57:406–412

    PubMed  CAS  Google Scholar 

  49. Bertos NR, Wang AH, Yang XJ (2001) Class II histone deacetylases: structure, function, and regulation. Biochem Cell Biol 79:243–252

    PubMed  CAS  Google Scholar 

  50. Fischle W, Kiermer V, Dequiedt F, Verdin E (2001) The emerging role of class II histone deacetylases. Biochem Cell Biol 79:337–348

    PubMed  CAS  Google Scholar 

  51. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A et al (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458

    PubMed  CAS  Google Scholar 

  52. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV et al (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18:601–607

    PubMed  CAS  Google Scholar 

  53. Aldana-Masangkay GI, Sakamoto KM (2011) The role of HDAC6 in cancer. J Biomed Biotechnol 2011:875824

    PubMed  Google Scholar 

  54. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749

    PubMed  Google Scholar 

  55. Verdin E, Dequiedt F, Kasler HG (2003) Class II histone deacetylases: versatile regulators. Trends Genet 19:286–293

    PubMed  CAS  Google Scholar 

  56. Grozinger CM, Hassig CA, Schreiber SL (1999) Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci USA 96:4868–4873

    PubMed  CAS  Google Scholar 

  57. Mahlknecht U, Schnittger S, Landgraf F, Schoch C, Ottmann OG, Hiddemann W et al (2001) Assignment of the human histone deacetylase 6 gene (HDAC6) to X chromosome p11.23 by in situ hybridization. Cytogenet Cell Genet 93:135–136

    PubMed  CAS  Google Scholar 

  58. Verdel A, Khochbin S (1999) Identification of a new family of higher eukaryotic histone deacetylases. Coordinate expression of differentiation-dependent chromatin modifiers. J Biol Chem 274:2440–2445

    PubMed  CAS  Google Scholar 

  59. Boyault C, Sadoul K, Pabion M, Khochbin S (2007) HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene 26:5468–5476

    PubMed  CAS  Google Scholar 

  60. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP (2003) The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115:727–738

    PubMed  CAS  Google Scholar 

  61. Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, Koomen J et al (2007) HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 27:197–213

    PubMed  CAS  Google Scholar 

  62. Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D et al (2002) In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J 21:6820–6831

    PubMed  CAS  Google Scholar 

  63. Murphy PJ, Morishima Y, Kovacs JJ, Yao TP, Pratt WB (2005) Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chaperone. J Biol Chem 280:33792–33799

    PubMed  CAS  Google Scholar 

  64. Aoyagi S, Archer TK (2005) Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends Cell Biol 15:565–567

    PubMed  CAS  Google Scholar 

  65. Bali P, Pranpat M, Bradner J, Balasis M, Fiskus W, Guo F et al (2005) Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 280:26729–26734

    PubMed  CAS  Google Scholar 

  66. Kekatpure VD, Dannenberg AJ, Subbaramaiah K (2009) HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl hydrocarbon receptor signaling. J Biol Chem 284:7436–7445

    PubMed  CAS  Google Scholar 

  67. Basak S, Pookot D, Noonan EJ, Dahiya R (2008) Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function. Mol Cancer Ther 7:3195–3202

    PubMed  CAS  Google Scholar 

  68. Fang Y, Fliss AE, Robins DM, Caplan AJ (1996) Hsp90 regulates androgen receptor hormone binding affinity in vivo. J Biol Chem 271:28697–28702

    PubMed  CAS  Google Scholar 

  69. Ai J, Wang Y, Dar JA, Liu J, Liu L, Nelson JB et al (2009) HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-­resistant prostate cancer. Mol Endocrinol 23:1963–1972

    PubMed  CAS  Google Scholar 

  70. Guardiola AR, Yao TP (2002) Molecular cloning and characterization of a novel histone deacetylase HDAC10. J Biol Chem 277:3350–3356

    PubMed  CAS  Google Scholar 

  71. Georget V, Lobaccaro JM, Terouanne B, Mangeat P, Nicolas JC, Sultan C (1997) Trafficking of the androgen receptor in living cells with fused green fluorescent protein-androgen receptor. Mol Cell Endocrinol 129:17–26

    PubMed  CAS  Google Scholar 

  72. Hager GL, Lim CS, Elbi C, Baumann CT (2000) Trafficking of nuclear receptors in living cells. J Steroid Biochem Mol Biol 74:249–254

    PubMed  CAS  Google Scholar 

  73. Nakauchi H, Matsuda K, Ochiai I, Kawauchi A, Mizutani Y, Miki T et al (2007) A differential ligand-mediated response of green fluorescent protein-tagged androgen receptor in living prostate cancer and non-prostate cancer cell lines. J Histochem Cytochem 55:535–544

    PubMed  CAS  Google Scholar 

  74. Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25:276–308

    PubMed  CAS  Google Scholar 

  75. Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM et al (1983) LNCaP model of human prostatic carcinoma. Cancer Res 43:1809–1818

    PubMed  CAS  Google Scholar 

  76. Lee C, Sutkowski DM, Sensibar JA, Zelner D, Kim I, Amsel I et al (1995) Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136:796–803

    PubMed  CAS  Google Scholar 

  77. Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M et al (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop ­normally. Mol Cell Biol 28:1688–1701

    PubMed  CAS  Google Scholar 

  78. Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K et al (2007) An ­acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 25:151–159

    PubMed  CAS  Google Scholar 

  79. Gibbs A, Schwartzman J, Deng V, Alumkal J (2009) Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci USA 106:16663–16668

    PubMed  CAS  Google Scholar 

  80. Chen L, Meng S, Wang H, Bali P, Bai W, Li B et al (2005) Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824. Mol Cancer Ther 4:1311–1319

    PubMed  CAS  Google Scholar 

  81. Culig Z (2004) Androgen receptor cross-talk with cell signalling pathways. Growth Factors 22:179–184

    PubMed  CAS  Google Scholar 

  82. Kaarbo M, Klokk TI, Saatcioglu F (2007) Androgen signaling and its interactions with other signaling pathways in prostate cancer. Bioessays 29:1227–1238

    PubMed  Google Scholar 

  83. Li Y, Zhang X, Polakiewicz RD, Yao TP, Comb MJ (2008) HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem 283:12686–12690

    PubMed  CAS  Google Scholar 

  84. Tran AD, Marmo TP, Salam AA, Che S, Finkelstein E, Kabarriti R et al (2007) HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J Cell Sci 120:1469–1479

    PubMed  CAS  Google Scholar 

  85. Nakagawa M, Oda Y, Eguchi T, Aishima S, Yao T, Hosoi F et al (2007) Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep 18:769–774

    PubMed  CAS  Google Scholar 

  86. Waltregny D, North B, Van Mellaert F, de Leval J, Verdin E, Castronovo V (2004) Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells. Eur J Histochem 48:273–290

    PubMed  CAS  Google Scholar 

  87. Kim IA, No M, Lee JM, Shin JH, Oh JS, Choi EJ et al (2009) Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: potential role of histone deacetylase 6. Radiother Oncol 92:125–132

    PubMed  CAS  Google Scholar 

  88. Lee YS, Lim KH, Guo X, Kawaguchi Y, Gao Y, Barrientos T et al (2008) The cytoplasmic deacetylase HDAC6 is required for efficient oncogenic tumorigenesis. Cancer Res 68:7561–7569

    PubMed  CAS  Google Scholar 

  89. Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F (2008) HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 18:291–297

    PubMed  CAS  Google Scholar 

  90. Wu Y, Song SW, Sun J, Bruner JM, Fuller GN, Zhang W (2010) IIp45 inhibits cell migration through inhibition of HDAC6. J Biol Chem 285:3554–3560

    PubMed  CAS  Google Scholar 

  91. Wickstrom SA, Masoumi KC, Khochbin S, Fassler R, Massoumi R (2010) CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin. EMBO J 29:131–144

    PubMed  Google Scholar 

  92. Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784

    PubMed  CAS  Google Scholar 

  93. Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK (2001) Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1:194–202

    PubMed  CAS  Google Scholar 

  94. Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C et al (2007) Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 109:31–39

    PubMed  CAS  Google Scholar 

  95. Wagner JM, Hackanson B, Lubbert M, Jung M (2010) Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin Epigenetics 1:117–136

    PubMed  CAS  Google Scholar 

  96. Welsbie DS, Xu J, Chen Y, Borsu L, Scher HI, Rosen N et al (2009) Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer. Cancer Res 69:958–966

    PubMed  CAS  Google Scholar 

  97. Marrocco DL, Tilley WD, Bianco-Miotto T, Evdokiou A, Scher HI, Rifkind RA et al (2007) Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell ­proliferation. Mol Cancer Ther 6:51–60

    PubMed  CAS  Google Scholar 

  98. Rokhlin OW, Glover RB, Guseva NV, Taghiyev AF, Kohlgraf KG, Cohen MB (2006) Mechanisms of cell death induced by histone deacetylase inhibitors in androgen receptor-­positive prostate cancer cells. Mol Cancer Res 4:113–123

    PubMed  CAS  Google Scholar 

  99. Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B (2008) Fruit, vegetable, vitamin a intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis 11:61–66

    PubMed  CAS  Google Scholar 

  100. Cohen JH, Kristal AR, Stanford JL (2000) Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 92:61–68

    PubMed  CAS  Google Scholar 

  101. Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR et al (2000) Vegetables, fruits, legumes and prostate cancer: a multiethnic case–control study. Cancer Epidemiol Biomarkers Prev 9:795–804

    PubMed  CAS  Google Scholar 

  102. Kristal AR, Lampe JW (2002) Brassica vegetables and prostate cancer risk: a review of the epidemiological evidence. Nutr Cancer 42:1–9

    PubMed  Google Scholar 

  103. Myzak MC, Karplus PA, Chung FL, Dashwood RH (2004) A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res 64:5767–5774

    PubMed  CAS  Google Scholar 

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Ai, J., Wang, Z. (2013). HDAC6 Regulation of Androgen Signaling in Prostate Cancer. In: Tindall, D. (eds) Prostate Cancer. Protein Reviews, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6828-8_16

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