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Androgen Action, Wnt Signaling, and Prostate Tumorigenesis

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Androgen-Responsive Genes in Prostate Cancer
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Abstract

Androgen signaling is mainly mediated through AR and plays a critical role in prostate tumorigenesis. Current studies have shown that AR-mediated transcription is facilitated through direct or indirect interactions with different signaling pathways and coregulators. The Wnt signaling pathway and its key component, β-catenin, are critical in embryonic development and tumorigenesis. Emerging evidence suggests a promotional role of the Wnt and β-catenin signaling pathway in prostate cancer development and progression. The discovery of the interaction between AR and β-catenin provides the molecular basis for crosstalk between androgen and Wnt signaling. It has been shown that mutations in adenomatous polyposis coli (APC), β-catenin, and other components of the β-catenin destruction complex are rare in prostate cancer cells. Therefore, the molecular mechanisms underlying β-catenin oncogenic activation in prostate cancer may be different from those observed in human colorectal cancer or other malignancies. Further study of the role and regulation of Wnt signaling and β-catenin should provide fresh insight into our current knowledge of androgen action and prostate tumorigenesis, which may lead to the development of novel therapeutic strategies for prostate cancer patients.

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References

  1. Balk SP (2002) Androgen receptor as a target in androgen-independent prostate cancer. Urology 60(3 Suppl 1):132–138, discussion 138–139

    Article  PubMed  Google Scholar 

  2. Gelmann EP (2002) Molecular biology of the androgen receptor. J Clin Oncol 20(13):3001–3015

    Article  PubMed  CAS  Google Scholar 

  3. Huggins C, Hodges CV (2002) Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol 168(1):9–12

    Article  PubMed  Google Scholar 

  4. Jenster G (1999) The role of the androgen receptor in the development and progression of prostate cancer. Semin Oncol 26(4):407–421

    PubMed  CAS  Google Scholar 

  5. Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1(1):34–45

    Article  PubMed  CAS  Google Scholar 

  6. Nusse R (2003) Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development 130(22):5297–5305

    Article  PubMed  CAS  Google Scholar 

  7. Polakis P (2000) Wnt signaling and cancer. Genes Dev 14(15):1837–1851

    PubMed  CAS  Google Scholar 

  8. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  PubMed  CAS  Google Scholar 

  9. He X, Semenov M, Tamai K, Zeng X (2004) LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development 131(8):1663–1677

    Article  PubMed  CAS  Google Scholar 

  10. Hsieh JC (2004) Specificity of WNT-receptor interactions. Front Biosci 9:1333–1338

    Article  PubMed  CAS  Google Scholar 

  11. Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116(Pt 13):2627–2634

    Article  PubMed  CAS  Google Scholar 

  12. Pandur P, Maurus D, Kuhl M (2002) Increasingly complex: new players enter the Wnt signaling network. Bioessays 24(10):881–884

    Article  PubMed  CAS  Google Scholar 

  13. Nusse R (2005) Wnt signaling in disease and in development. Cell Res 15(1):28–32

    Article  PubMed  CAS  Google Scholar 

  14. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, Alkalay I (2002) Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16(9):1066–1076

    Article  PubMed  CAS  Google Scholar 

  15. Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P (1998) Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol 8 (10):573–581

    Google Scholar 

  16. Latres E, Chiaur DS, Pagano M (1999) The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene 18(4):849–854

    Article  PubMed  CAS  Google Scholar 

  17. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) Beta-catenin is a target for the ubiquitin-proteasome pathway. Embo J 16(13):3797–3804

    Article  PubMed  CAS  Google Scholar 

  18. Eastman Q, Grosschedl R (1999) Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 11(2):233–240

    Article  PubMed  CAS  Google Scholar 

  19. Veeman MT, Axelrod JD, Moon RT (2003) A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell 5(3):367–377

    Article  PubMed  CAS  Google Scholar 

  20. Slusarski DC, Yang-Snyder J, Busa WB, Moon RT (1997) Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev Biol 182(1):114–120

    Article  PubMed  CAS  Google Scholar 

  21. Yamanaka H, Moriguchi T, Masuyama N, Kusakabe M, Hanafusa H, Takada R, Takada S, Nishida E (2002) JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. EMBO Rep 3(1):69–75

    Article  PubMed  CAS  Google Scholar 

  22. Boutros M, Paricio N, Strutt DI, Mlodzik M (1998) Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94(1):109–118

    Article  PubMed  CAS  Google Scholar 

  23. Mulholland DJ, Cheng H, Reid K, Rennie PS, Nelson CC (2002) The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli. J Biol Chem 277(20):17933–17943

    Article  PubMed  CAS  Google Scholar 

  24. Truica CI, Byers S, Gelmann EP (2000) Beta-catenin affects androgen receptor transcriptional activity and ligand specificity. Cancer Res 60(17):4709–4713

    PubMed  CAS  Google Scholar 

  25. Chesire DR, Isaacs WB (2003) Beta-catenin signaling in prostate cancer: an early perspective. Endocr Relat Cancer 10(4):537–560

    Article  PubMed  CAS  Google Scholar 

  26. Yang F, Li X, Sharma M, Sasaki CY, Longo DL, Lim B, Sun Z (2002) Linking beta-catenin to androgen-signaling pathway. J Biol Chem 277(13):11336–11344

    Article  PubMed  CAS  Google Scholar 

  27. Chen G, Shukeir N, Potti A, Sircar K, Aprikian A, Goltzman D, Rabbani SA (2004) Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer 101(6):1345–1356

    Article  PubMed  CAS  Google Scholar 

  28. Kirikoshi H, Sekihara H, Katoh M (2001) Molecular cloning and characterization of human WNT7B. Int J Oncol 19(4):779–783

    PubMed  CAS  Google Scholar 

  29. Zhu H, Mazor M, Kawano Y, Walker MM, Leung HY, Armstrong K, Waxman J, Kypta RM (2004) Analysis of Wnt gene expression in prostate cancer: mutual inhibition by WNT11 and the androgen receptor. Cancer Res 64(21):7918–7926

    Article  PubMed  CAS  Google Scholar 

  30. Takahashi S, Watanabe T, Okada M, Inoue K, Ueda T, Takada I, Watabe T, Yamamoto Y, Fukuda T, Nakamura T, Akimoto C, Fujimura T, Hoshino M, Imai Y, Metzger D, Miyazono K, Minami Y, Chambon P, Kitamura T, Matsumoto T, Kato S (2011) Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer. Proc Natl Acad Sci U S A 108(12):4938–4943. doi:1014850108 [pii] 10.1073/pnas.1014850108

    Article  PubMed  CAS  Google Scholar 

  31. Sagara N, Toda G, Hirai M, Terada M, Katoh M (1998) Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7. Biochem Biophys Res Commun 252(1):117–122

    Article  PubMed  CAS  Google Scholar 

  32. Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M (1999) Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21. Biochem Biophys Res Commun 264(3):955–961

    Article  PubMed  CAS  Google Scholar 

  33. Tokuhara M, Hirai M, Atomi Y, Terada M, Katoh M (1998) Molecular cloning of human Frizzled-6. Biochem Biophys Res Commun 243(2):622–627

    Article  PubMed  CAS  Google Scholar 

  34. Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, Kristiansen G, Hsieh JC, Hofstaedter F, Hartmann A, Knuechel R, Rosenthal A, Pilarsky C (2003) WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. J Pathol 201(2):204–212

    Article  PubMed  CAS  Google Scholar 

  35. Joesting MS, Cheever TR, Volzing KG, Yamaguchi TP, Wolf V, Naf D, Rubin JS, Marker PC (2008) Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate. Dev Biol 317(1):161–173. doi:S0012-1606(08)00119-X [pii]10.1016/j.ydbio.2008.02.021

    Article  PubMed  CAS  Google Scholar 

  36. Placencio VR, Sharif-Afshar AR, Li X, Huang H, Uwamariya C, Neilson EG, Shen MM, Matusik RJ, Hayward SW, Bhowmick NA (2008) Stromal transforming growth factor-beta signaling mediates prostatic response to androgen ablation by paracrine Wnt activity. Cancer Res 68(12):4709–4718. doi:68/12/4709 [pii] 10.1158/0008-5472.CAN-07-6289

    Article  PubMed  CAS  Google Scholar 

  37. Verras M, Brown J, Li X, Nusse R, Sun Z (2004) Wnt3a growth factor induces androgen receptor-mediated transcription and enhances cell growth in human prostate cancer cells. Cancer Res 64(24):8860–8866

    Article  PubMed  CAS  Google Scholar 

  38. Shibamoto S, Higano K, Takada R, Ito F, Takeichi M, Takada S (1998) Cytoskeletal reorganization by soluble Wnt-3a protein signalling. Genes Cells 3(10):659–670

    Article  PubMed  CAS  Google Scholar 

  39. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275(5307):1784–1787

    Article  PubMed  CAS  Google Scholar 

  40. Gerstein AV, Almeida TA, Zhao G, Chess E, Shih Ie M, Buhler K, Pienta K, Rubin MA, Vessella R, Papadopoulos N (2002) APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer 34(1):9–16

    Article  PubMed  CAS  Google Scholar 

  41. Voeller HJ, Truica CI, Gelmann EP (1998) Beta-catenin mutations in human prostate cancer. Cancer Res 58(12):2520–2523

    PubMed  CAS  Google Scholar 

  42. Chesire DR, Ewing CM, Sauvageot J, Bova GS, Isaacs WB (2000) Detection and analysis of beta-catenin mutations in prostate cancer. Prostate 45(4):323–334

    Article  PubMed  CAS  Google Scholar 

  43. Chesire DR, Ewing CM, Gage WR, Isaacs WB (2002) In vitro evidence for complex modes of nuclear beta-catenin signaling during prostate growth and tumorigenesis. Oncogene 21(17):2679–2694

    Article  PubMed  CAS  Google Scholar 

  44. de la Taille A, Rubin MA, Chen MW, Vacherot F, de Medina SG, Burchardt M, Buttyan R, Chopin D (2003) Beta-catenin-related anomalies in apoptosis-resistant and hormone-refractory prostate cancer cells. Clin Cancer Res 9(5):1801–1807

    PubMed  Google Scholar 

  45. Pawlowski JE, Ertel JR, Allen MP, Xu M, Butler C, Wilson EM, Wierman ME (2002) Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells. J Biol Chem 277(23):20702–20710

    Article  PubMed  CAS  Google Scholar 

  46. Song LN, Herrell R, Byers S, Shah S, Wilson EM, Gelmann EP (2003) Beta-catenin binds to the activation function 2 region of the androgen receptor and modulates the effects of the N-terminal domain and TIF2 on ligand-dependent transcription. Mol Cell Biol 23(5):1674–1687

    Article  PubMed  CAS  Google Scholar 

  47. Levy L, Wei Y, Labalette C, Wu Y, Renard CA, Buendia MA, Neuveut C (2004) Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction. Mol Cell Biol 24(8):3404–3414

    Article  PubMed  CAS  Google Scholar 

  48. Huber AH, Nelson WJ, Weis WI (1997) Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 90(5):871–882

    Article  PubMed  CAS  Google Scholar 

  49. Yumoto F, Nguyen P, Sablin EP, Baxter JD, Webb P, Fletterick RJ (2012) Structural basis of coactivation of liver receptor homolog-1 by beta-catenin. Proc Natl Acad Sci U S A 109(1):143–148. doi:1117036108 [pii]10.1073/pnas.1117036108

    Article  PubMed  CAS  Google Scholar 

  50. Zhuo M, Zhu C, Sun J, Weis WI, Sun Z (2011) The beta-catenin binding protein ICAT modulates androgen receptor activity. Mol Endocrinol 25(10):1677–1688. doi:me.2011-1023 [pii]10.1210/me.2011-1023

    Article  PubMed  CAS  Google Scholar 

  51. Li H, Kim JH, Koh SS, Stallcup MR (2004) Synergistic effects of coactivators GRIP1 and beta-catenin on gene activation: cross-talk between androgen receptor and Wnt signaling pathways. J Biol Chem 279(6):4212–4220

    Article  PubMed  CAS  Google Scholar 

  52. Koh SS, Li H, Lee YH, Widelitz RB, Chuong CM, Stallcup MR (2002) Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators. J Biol Chem 277(29):26031–26035

    Article  PubMed  CAS  Google Scholar 

  53. Labalette C, Renard CA, Neuveut C, Buendia MA, Wei Y (2004) Interaction and functional cooperation between the LIM protein FHL2, CBP/p300, and beta-catenin. Mol Cell Biol 24(24):10689–10702

    Article  PubMed  CAS  Google Scholar 

  54. Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (2004) Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells. Mol Endocrinol 18(10):2388–2401

    Article  PubMed  CAS  Google Scholar 

  55. Song LN, Coghlan M, Gelmann EP (2004) Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor. Mol Endocrinol 18(1):70–85

    Article  PubMed  CAS  Google Scholar 

  56. Wang G, Wang J, Sadar MD (2008) Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer. Cancer Res 68(23):9918–9927

    Article  PubMed  CAS  Google Scholar 

  57. Kyprianou N, Isaacs JT (1988) Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122(2):552–562

    Article  PubMed  CAS  Google Scholar 

  58. Sandford NL, Searle JW, Kerr JF (1984) Successive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation. Pathology 16(4):406–410

    Article  PubMed  CAS  Google Scholar 

  59. Kerr JF, Searle J (1973) Deletion of cells by apoptosis during castration-induced involution of the rat prostate. Virchows Arch B Cell Pathol 13(2):87–102

    PubMed  CAS  Google Scholar 

  60. Gounari F, Signoretti S, Bronson R, Klein L, Sellers WR, Kum J, Siermann A, Taketo MM, von Boehmer H, Khazaie K (2002) Stabilization of beta-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia. Oncogene 21(26):4099–4107

    Article  PubMed  CAS  Google Scholar 

  61. Bierie B, Nozawa M, Renou JP, Shillingford JM, Morgan F, Oka T, Taketo MM, Cardiff RD, Miyoshi K, Wagner KU, Robinson GW, Hennighausen L (2003) Activation of beta-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation. Oncogene 22(25):3875–3887

    Article  PubMed  CAS  Google Scholar 

  62. Bruxvoort KJ, Charbonneau HM, Giambernardi TA, Goolsby JC, Qian CN, Zylstra CR, Robinson DR, Roy-Burman P, Shaw AK, Buckner-Berghuis BD, Sigler RE, Resau JH, Sullivan R, Bushman W, Williams BO (2007) Inactivation of Apc in the mouse prostate causes prostate carcinoma. Cancer Res 67(6):2490–2496

    Article  PubMed  CAS  Google Scholar 

  63. Kojima S, Inahara M, Suzuki H, Ichikawa T, Furuya Y (2009) Implications of insulin-like growth factor-I for prostate cancer therapies. Int J Urol 16(2):161–167. doi:IJU2224 [pii]10.1111/j.1442-2042.2008.02224.x

    Article  PubMed  CAS  Google Scholar 

  64. Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54(20):5474–5478

    PubMed  CAS  Google Scholar 

  65. Playford MP, Bicknell D, Bodmer WF, Macaulay VM (2000) Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci U S A 97(22):12103–12108

    Article  PubMed  CAS  Google Scholar 

  66. Verras M, Sun Z (2005) Beta-catenin is involved in insulin-like growth factor 1-mediated transactivation of the androgen receptor. Mol Endocrinol 19(2):391–398

    Article  PubMed  CAS  Google Scholar 

  67. Liu X, Choi RY, Jawad SM, Arnold JT (2011) Androgen-induced PSA expression requires not only activation of AR but also endogenous IGF-I or IGF-I/PI3K/Akt signaling in human prostate cancer epithelial cells. Prostate 71(7):766–777. doi:10.1002/pros.21293

    Article  PubMed  CAS  Google Scholar 

  68. Wen Y, Hu MC, Makino K, Spohn B, Bartholomeusz G, Yan DH, Hung MC (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res 60(24):6841–6845

    PubMed  CAS  Google Scholar 

  69. Carson JP, Kulik G, Weber MJ (1999) Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res 59(7):1449–1453

    PubMed  CAS  Google Scholar 

  70. Sharma M, Chuang WW, Sun Z (2002) Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. J Biol Chem 277(34):30935–30941

    Article  PubMed  CAS  Google Scholar 

  71. Shen MM, Abate-Shen C (2007) Pten inactivation and the emergence of androgen-independent prostate cancer. Cancer Res 67(14):6535–6538

    Article  PubMed  CAS  Google Scholar 

  72. Wu X, Senechal K, Neshat MS, Whang YE, Sawyers CL (1998) The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 95(26):15587–15591

    Article  PubMed  CAS  Google Scholar 

  73. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, Scardino PT, Rosen N, Sawyers CL (2011) Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19(5):575–586. doi:S1535-6108(11)00155-3 [pii]10.1016/j.ccr.2011.04.008

    Article  PubMed  CAS  Google Scholar 

  74. Mulholland DJ, Tran LM, Li Y, Cai H, Morim A, Wang S, Plaisier S, Garraway IP, Huang J, Graeber TG, Wu H (2011) Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell 19(6):792–804. doi:S1535-6108(11)00164-4 [pii]10.1016/j.ccr.2011.05.006

    Article  PubMed  CAS  Google Scholar 

  75. Mulholland DJ, Dedhar S, Wu H, Nelson CC (2006) PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer. Oncogene 25(3):329–337

    Article  PubMed  CAS  Google Scholar 

  76. Ohigashi T, Mizuno R, Nakashima J, Marumo K, Murai M (2005) Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells. Prostate 62(1):61–68

    Article  PubMed  CAS  Google Scholar 

  77. Salas TR, Kim J, Vakar-Lopez F, Sabichi AL, Troncoso P, Jenster G, Kikuchi A, Chen SY, Shemshedini L, Suraokar M, Logothetis CJ, DiGiovanni J, Lippman SM, Menter DG (2004) Glycogen synthase kinase-3 beta is involved in the phosphorylation and suppression of androgen receptor activity. J Biol Chem 279(18):19191–19200

    Article  PubMed  CAS  Google Scholar 

  78. Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (2004) Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells. J Biol Chem 279(31):32444–32452

    Article  PubMed  CAS  Google Scholar 

  79. Roose J, Clevers H (1999) TCF transcription factors: molecular switches in carcinogenesis. Biochim Biophys Acta 1424(2–3):M23–37

    PubMed  CAS  Google Scholar 

  80. Chesire DR, Isaacs WB (2002) Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene 21(55):8453–8469

    Article  PubMed  CAS  Google Scholar 

  81. Mulholland DJ, Read JT, Rennie PS, Cox ME, Nelson CC (2003) Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis. Oncogene 22(36):5602–5613

    Article  PubMed  CAS  Google Scholar 

  82. Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T (2000) Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev 14(14):1741–1749

    PubMed  CAS  Google Scholar 

  83. Tutter AV, Fryer CJ, Jones KA (2001) Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro. Genes Dev 15(24):3342–3354. doi:10.1101/gad.946501

    Article  PubMed  CAS  Google Scholar 

  84. Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP (2003) A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem 278(33):30828–30834

    Article  PubMed  CAS  Google Scholar 

  85. Birchmeier W, Hulsken J, Behrens J (1995) Adherens junction proteins in tumour progression. Cancer Surv 24:129–140

    PubMed  CAS  Google Scholar 

  86. Huber AH, Weis WI (2001) The Structure of the beta-Catenin/E-Cadherin Complex and the Molecular Basis of Diverse Ligand Recognition by beta-Catenin. Cell 105(3):391–402

    Article  PubMed  CAS  Google Scholar 

  87. Umbas R, Schalken JA, Aalders TW, Carter BS, Karthaus HF, Schaafsma HE, Debruyne FM, Isaacs WB (1992) Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res 52(18):5104–5109

    PubMed  CAS  Google Scholar 

  88. Paul R, Ewing CM, Jarrard DF, Isaacs WB (1997) The cadherin cell-cell adhesion pathway in prostate cancer progression. Br J Urol 79(Suppl 1):37–43

    PubMed  Google Scholar 

  89. Bussemakers MJ, van Moorselaar RJ, Giroldi LA, Ichikawa T, Isaacs JT, Takeichi M, Debruyne FM, Schalken JA (1992) Decreased expression of E-cadherin in the progression of rat prostatic cancer. Cancer Res 52(10):2916–2922

    PubMed  CAS  Google Scholar 

  90. Richmond PJ, Karayiannakis AJ, Nagafuchi A, Kaisary AV, Pignatelli M (1997) Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res 57(15):3189–3193

    PubMed  CAS  Google Scholar 

  91. Luo J, Lubaroff DM, Hendrix MJ (1999) Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection. Cancer Res 59(15):3552–3556

    PubMed  CAS  Google Scholar 

  92. Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 55(22):5195–5199

    PubMed  CAS  Google Scholar 

  93. Mitchell S, Abel P, Ware M, Stamp G, Lalani E (2000) Phenotypic and genotypic characterization of commonly used human prostatic cell lines. BJU Int 85(7):932–944

    Article  PubMed  CAS  Google Scholar 

  94. Nelson WJ, Nusse R (2004) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303(5663):1483–1487

    Article  PubMed  CAS  Google Scholar 

  95. Sasaki CY, Lin H, Morin PJ, Longo DL (2000) Truncation of the extracellular region abrogrates cell contact but retains the growth-suppressive activity of E-cadherin. Cancer Res 60(24):7057–7065

    PubMed  CAS  Google Scholar 

  96. van de Wetering M, Barker N, Harkes IC, van der Heyden M, Dijk NJ, Hollestelle A, Klijn JG, Clevers H, Schutte M (2001) Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling. Cancer Res 61(1):278–284

    PubMed  Google Scholar 

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Acknowledgment

This article was supported by National Institutes of Health Grants CA070297 and CA151623.

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Correspondence to Zijie Sun .

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Sun, Z., Lee, S.H. (2013). Androgen Action, Wnt Signaling, and Prostate Tumorigenesis. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_7

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