The role of transcription factors in prostate cancer and potential for future RNA interference therapy

Expert Opinion on Therapeutic Targets

Volumn 18, Issue 6, 2014, Pages 633-649

  Fitzgerald, Kathleen A ^a   Evans, James C ^a   McCarthy, Joanna ^a   Guo, Jianfeng ^a   Prencipe, Maria ^b   Kearney, Meghan ^a   Watson, William R ^a   O'Driscoll, Caitriona M ^a,b  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

Activator protein 1; Androgen receptor; Delivery of RNAi; EIF4E; Forkhead box M1; Gene therapy; Nuclear factor B; Prostate cancer; RNA interference; Serum response factor; Signal transducer and activator of transcription; Specificity protein 1; Transcription factor; Y box binding protein 1

Indexed keywords

ANDROGEN RECEPTOR; INITIATION FACTOR 4E; NUCLEAR FACTOR; SERUM RESPONSE FACTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR SP1; Y BOX BINDING PROTEIN 1; ANTIANDROGEN; FORKHEAD TRANSCRIPTION FACTOR; FOXM1 PROTEIN, HUMAN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; STAT PROTEIN;

ANDROGEN DEPRIVATION THERAPY; CANCER CHEMOTHERAPY; CANCER GENE THERAPY; DRUG TARGETING; METASTASIS; PROSTATE CANCER; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; GENETICS; HUMAN; MALE; METABOLISM; PHYSIOLOGY; PROSTATIC NEOPLASMS;

ANDROGEN ANTAGONISTS; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; MALE; NF-KAPPA B; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN; RNA INTERFERENCE; SERUM RESPONSE FACTOR; STAT TRANSCRIPTION FACTORS; TRANSCRIPTION FACTOR AP-1; TRANSCRIPTION FACTORS;

EID: 84900816295     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2014.896904     Document Type: Review

References (138)

1. Jemal A, Siegel R, Xu J, et al. Cancer Statistics, 2010. CA Cancer J Clin 2010;60(5):277-300
2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63(1):11-30
3. No authors listed. Management of localised prostate cancer: watchful waiting, surgery or radiation therapy, depending on the natural course, which is often relatively slow. Prescrire Int 2012;21(131):242-8
4. Devlin HL, Mudryj M. Progression of prostate cancer: multiple pathways to androgen independence. Cancer Lett 2009;274(2):177-86
5. Heinlein CA, Chang CS. Androgen receptor in prostate cancer. Endocr Rev 2004;25(2):276-308
6. Bennett NC, Gardiner RA, Hooper JD, et al. Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol 2010;42(6):813-27
7. Shelley M, Mason MD. Docetaxel plus prednisone improves survival in men with advanced prostate cancer. Cancer Treat Rev 2005;31(5):403-7
8. Jain G, Cronauer MV, Schrader M, et al. NF-kappaB signaling in prostate cancer: a promising therapeutic target? World J Urol 2012;30(3):303-10
9. Horwich A, Hugosson J, de Reijke T, et al. Prostate cancer: ESMO consensus conference guidelines 2012. Ann Oncol 2013;24(5):1141-62
10. Attard G, Belldegrun AS, de Bono JS. Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer. BJU Int 2005;96(9):1241-6
11. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368(2):138-48
12. Higano CS. New treatment options for patients with metastatic castration-resistant prostate cancer. Cancer Treat Rev 2012;38(5):340-5
13. Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351(15):1513-20
14. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351(15):1502-12
15. Hwang C. Overcoming docetaxel resistance in prostate cancer: a perspective review. Ther Adv Med Oncol 2012;4(6):329-40
16. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364(21):1995-2005
17. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376(9747):1147-54
18. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367(13):1187-97
19. Li Y, Chan SC, Brand LJ, et al. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res 2013;73(2):483-9
20. Omlin A, de Bono JS. Therapeutic options for advanced prostate cancer: 2011 update. Curr Urol Rep 2012;13(2):170-8
21. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377(9768):813-22
22. Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet 2007;8(3):173-84
23. Bushati N, Cohen SM. MicroRNA functions. Annu Rev Cell Dev Biol 2007;23:175-205
24. Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov 2010;9(1):57-67
25. Guo J, Bourre L, Soden DM, et al. Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics? Biotechnol Adv 2011;29(4):402-17
26. Devi GR. siRNA-based approaches in cancer therapy. Cancer Gene Ther 2006;13(9):819-29
27. de Fougerolles A, Vornlocher HP, Maraganore J, et al. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 2007;6(6):443-53
28. Wang W, Li W, Ma N, et al. Non-viral gene delivery methods. Curr Pharm Biotechnol 2013;14(1):46-60
29. Guo J, Evans JC, O'Driscoll CM. Delivering RNAi therapeutics with non-viral technology: a promising strategy for prostate cancer? Trends Mol Med 2013;19(4):250-61
30. Lv H, Zhang S, Wang B, et al. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 2006;114(1):100-9
31. Kaiser PK, Symons RC, Shah SM, et al. RNAi-based treatment for neovascular age-related macular degeneration by Sirna-027. Am J Ophthalmol 2010;150(1):33-39.e2
32. Davis ME, Zuckerman JE, Choi CHJ, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010;464(7291):1067-U140
33. Guo J, Ogier JR, Desgranges S, et al. Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice. Biomaterials 2012;33(31):7775-84
34. Guo J, Cheng WP, Gu J, et al. Systemic delivery of therapeutic small interfering RNA using a pH-triggered amphiphilic poly-L-lysine nanocarrier to suppress prostate cancer growth in mice. Eur J Pharm Sci 2012;45(5):521-32
35. Latchman DS. Transcription factors: an overview. Int J Biochem Cell Biol 1997;29(12):1305-12
36. Pan Y, Tsai CJ, Ma B, et al. Mechanisms of transcription factor selectivity. Trends Genet 2010;26(2):75-83
37. Darnell JE. Transcription factors as targets for cancer therapy. Nat Rev Cancer 2002;2(10):740-9
38. Bumcrot D, Manoharan M, Koteliansky V, et al. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2006;2(12):711-19
39. Yun SJ, Yoon HY, Bae SC, et al. Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer. Prostate Cancer Prostatic Dis 2012;15(4):369-73
40. Li J, Al-Azzawi F. Mechanism of androgen receptor action. Maturitas 2009;63(2):142-8
41. Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol Cell 2002;9(3):601-10
42. Seruga B, Ocana A, Tannock IF. Drug resistance in metastatic castration-resistant prostate cancer. Nat Rev Clin Oncol 2011;8(1):12-23
43. Mostaghel EA, Montgomery B, Nelson PS. Castration-resistant prostate cancer: targeting androgen metabolic pathways in recurrent disease. Urol Oncol 2009;27(3):251-7
44. Santos AF, Huang H, Tindall DJ. The androgen receptor: a potential target for therapy of prostate cancer. Steroids 2004;69(2):79-85
45. Drachenberg DE, Elgamal AA, Rowbotham R, et al. Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate 1999;41(2):127-33
46. Hååg P, Bektic J, Bartsch G, et al. Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells. J Steroid Biochem Mol Biol 2005;96(3-4):251-8
47. Liao X, Tang S, Thrasher JB, et al. Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer. Mol Cancer Ther 2005;4(4):505-15
48. Wright ME, Tsai MJ, Aebersold R. Androgen receptor represses the neuroendocrine transdifferentiation process in prostate cancer cells. Mol Endocrinol 2003;17(9):1726-37
49. Yang Q, Fung KM, Day WV, et al. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival. Cancer Cell Int 2005;5(1):8
50. Snoek R, Cheng H, Margiotti K, et al. In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumors. Clin Cancer Res 2009;15(1):39-47
51. Cheng H, Snoek R, Ghaidi F, et al. Short hairpin RNA knockdown of the androgen receptor attenuates ligand-independent activation and delays tumor progression. Cancer Res 2006;66(21):10613-20
52. Compagno D, Merle C, Morin A, et al. SIRNA-directed in vivo silencing of androgen receptor inhibits the growth of castration-resistant prostate carcinomas. PLoS One 2007;2(10):e1006
53. Baud V, Karin M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 2009;8(1):33-40
54. Van Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 2007;13(4):1076-82
55. DiDonato JA, Mercurio F, Karin M. NF-kappaB and the link between inflammation and cancer. Immunol Rev 2012;246(1):379-400
56. Dolcet X, Llobet D, Pallares J, et al. NF-kappaB in development and progression of human cancer. Virchows Arch 2005;446(5):475-82
57. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature 2006;441(7092):431-6
58. Lessard L, Mes-Masson AM, Lamarre L, et al. NF-kappa B nuclear localization and its prognostic significance in prostate cancer. BJU Int 2003;91(4):417-20
59. Karin M, Lin A. NF-kappa B at the crossroads of life and death. Nat Immunol 2002;3(3):221-7
60. Micheau O, Lens S, Gaide O, et al. NF-kappaB signals induce the expression of c-FLIP. Mol Cell Biol 2001;21(16):5299-305
61. Romashkova JA, Makarov SS. NF-kappa B is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999;401(6748):86-90
62. Lee H, Herrmann A, Deng JH, et al. Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell 2009;15(4):283-93
63. Zhang L, Altuwaijri S, Deng F, et al. NF-kappaB regulates androgen receptor expression and prostate cancer growth. Am J Pathol 2009;175(2):489-99
64. Maxwell PJ, Gallagher R, Seaton A, et al. HIF-1 and NF-kappa B-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene 2007;26(52):7333-45
65. Xu Y, Fang F, Clair DKS, et al. Inverse relationship between PSA and IL-8 in prostate cancer: an insight into a NF-kappa B-mediated mechanism. PLoS One 2012;7(3):e32905
66. Fang Y, Sun H, Zhai J, et al. Antitumor activity of NF-kappaB decoy oligodeoxynucleotides in a prostate cancer cell line. Asian Pac J Cancer Prev 2011;12(10):2721-6
67. Xu Y, Josson S, Fang F, et al. RelB enhances prostate cancer growth: implications for the role of the nuclear factor-kappaB alternative pathway in tumorigenicity. Cancer Res 2009;69(8):3267-71
68. Codony-Servat J, Marin-Aguilera M, Visa L, et al. Nuclear factor-kappa B and interleukin-6 related docetaxel resistance in castration-resistant prostate cancer. Prostate 2013;73(5):512-21
69. Lai SY, Johnson FM. Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist Updat 2010;13(3):67-78
70. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci 2004;117(Pt 8):1281-3
71. Calo V, Migliavacca M, Bazan V, et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol 2003;197(2):157-68
72. Singh N, Hussain S, Bharadwaj M, et al. Overexpression of signal transducer and activator of transcription (STAT-3 and STAT-5) transcription factors and alteration of suppressor of cytokine signaling (SOCS-1) protein in prostate cancer. J Recept Signal Transduct Res 2012;32(6):321-7
73. Hsieh FC, Cheng G, Lin J. Evaluation of potential Stat3-regulated genes in human breast cancer. Biochem Biophys Res Commun 2005;335(2):292-9
74. Gu L, Vogiatzi P, Puhr M, et al. Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. Endocr Relat Cancer 2010;17(2):481-93
75. Yu H, Jove R. The STATs of cancer-new molecular targets come of age. Nat Rev Cancer 2004;4(2):97-105
76. Gu L, Dagvadorj A, Lutz J, et al. Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth. Am J Pathol 2010;176(4):1959-72
77. Michalaki V, Syrigos K, Charles P, et al. Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 2004;90(12):2312-16
78. Culig Z, Puhr M. Interleukin-6: a multifunctional targetable cytokine in human prostate cancer. Mol Cell Endocrinol 2012;360(1-2):52-8
79. Ni Z, Lou W, Leman ES, et al. Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells. Cancer Res 2000;60(5):1225-8
80. Lee SO, Lou W, Qureshi KM, et al. RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells. Prostate 2004;60(4):303-9
81. Zhou W, Grandis JR, Wells A. STAT3 is required but not sufficient for EGF receptor-mediated migration and invasion of human prostate carcinoma cell lines. Br J Cancer 2006;95(2):164-71
82. Gao LF, Zhang L, Hu JD, et al. Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo. Clin Cancer Res 2005;11(17):6333-41
83. Ahonen TJ, Xie J, LeBaron MJ, et al. Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol Chem 2003;278(29):27287-92
84. Li H, Ahonen TJ, Alanen K, et al. Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade. Cancer Res 2004;64(14):4774-82
85. Thomas C, Zoubeidi A, Kuruma H, et al. Transcription factor Stat5 knockdown enhances androgen receptor degradation and delays castration-resistant prostate cancer progression in vivo. Mol Cancer Ther 2011;10(2):347-59
86. Tan SH, Dagvadorj A, Shen F, et al. Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res 2008;68(1):236-48
87. Dagvadorj A, Kirken RA, Leiby B, et al. Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo. Clin Cancer Res 2008;14(5):1317-24
88. Halasi M, Gartel AL. Targeting FOXM1 in cancer. Biochem Pharmacol 2013;85(5):644-52
89. Pilarsky C, Wenzig M, Specht T, et al. Identification and validation of commonly overexpressed genes in solid tumors by comparison of microarray data. Neoplasia 2004;6(6):744-50
90. Chandran UR, Ma C, Dhir R, et al. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer 2007;7:64
91. Kalin TV, Wang IC, Ackerson TJ, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res 2006;66(3):1712-20
92. Li Q, Zhang N, Jia Z, et al. Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res 2009;69(8):3501-9
93. Yang C, Chen H, Yu L, et al. Inhibition of FOXM1 transcription factor suppresses cell proliferation and tumor growth of breast cancer. Cancer Gene Ther 2013;20(2):117-24
94. Teh MT, Wong ST, Neill GW, et al. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res 2002;62(16):4773-80
95. Laoukili J, Stahl M, Medema RH. FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta 2007;1775(1):92-102
96. Wang Z, Ahmad A, Li Y, et al. Forkhead box M1 transcription factor: a novel target for cancer therapy. Cancer Treat Rev 2010;36(2):151-6
97. Chen W, Yuan K, Tao ZZ, et al. Deletion of forkhead box M1 transcription factor reduces malignancy in laryngeal squamous carcinoma cells. Asian Pac J Cancer Prev 2011;12(7):1785-8
98. Bao B, Wang Z, Ali S, et al. Over-expression of FoxM1 leads to epithelial-mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells. J Cell Biochem 2011;112(9):2296-306
99. Okada K, Fujiwara Y, Takahashi T, et al. Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemoresistance for docetaxel in gastric cancer. Ann Surg Oncol 2013;20(3):1035-43
100. Wang Z, Banerjee S, Kong D, et al. Down-regulation of forkhead box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells. Cancer Res 2007;67(17):8293-300
101. Costa RWA (Oak Park, IL 60304, US), Wang, I-ching (727 W. Martin Luther King Drive 1005W, Cincinnati, OH 45220, US), inventor The Board of Trustees of the University of Illionis (352 Henry Administration Building 506 South Wright Street, Urbana, IL 61801, US), assignee. Methods of inhibiting tumor cell proliferation with FOXM1 siRNA 2011
102. Posern G, Treisman R. Actin' together: serum response factor, its cofactors and the link to signal transduction. Trends Cell Biol 2006;16(11):588-96
103. Heemers HV, Schmidt LJ, Sun Z, et al. Identification of a clinically relevant androgen-dependent gene signature in prostate cancer. Cancer Res 2011;71(5):1978-88
104. Chai J, Tarnawski AS. Serum response factor: discovery, biochemistry, biological roles and implications for tissue injury healing. J Physiol Pharmacol 2002;53(2):147-57
105. Heemers HV, Regan KM, Dehm SM, et al. Androgen induction of the androgen receptor coactivator four and a half LIM domain protein-2: evidence for a role for serum response factor in prostate cancer. Cancer Res 2007;67(21):10592-9
106. Prencipe M, Madden SF, O'Neill A, et al. Identification of transcription factors associated with castration-resistance: is the serum responsive factor a potential therapeutic target? Prostate 2013;73(7):743-53
107. Yu W, Feng S, Dakhova O, et al. FGFR-4 Arg(3)(8)(8) enhances prostate cancer progression via extracellular signal-related kinase and serum response factor signaling. Clin Cancer Res 2011;17(13):4355-66
108. Gorlov IP, Sircar K, Zhao H, et al. Prioritizing genes associated with prostate cancer development. BMC Cancer 2010;10:599
109. Verone AR, Duncan K, Godoy A, et al. Androgen-responsive serum response factor target genes regulate prostate cancer cell migration. Carcinogenesis 2013;34(8):1737-46
110. Kohno K, Izumi H, Uchiumi T, et al. The pleiotropic functions of the Y-box-binding protein, YB-1. BioEssays 2003;25(7):691-8
111. Lasham A, Print CG, Woolley AG, et al. YB-1: oncoprotein, prognostic marker and therapeutic target? Biochem J 2013;449(1):11-23
112. Kuwano M, Uchiumi T, Hayakawa H, et al. The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies. Cancer Sci 2003;94(1):9-14
113. Jurchott K, Bergmann S, Stein U, et al. YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression. J Biol Chem 2003;278(30):27988-96
114. Wu J, Lee C, Yokom D, et al. Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Res 2006;66(9):4872-9
115. Shiota M, Takeuchi A, Song Y, et al. Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression. Endocr Relat Cancer 2011;2011:18(4):505-17
116. Eliseeva IA, Kim ER, Guryanov SG, et al. Y-box-binding protein 1 (YB-1) and its functions. Biochemistry (Mosc) 2011;76(13):1402-33
117. Giménez-Bonafé P, Fedoruk MN, Whitmore TG, et al. YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. Prostate 2004;59(3):337-49
118. Safe S, Abdelrahim M. Sp transcription factor family and its role in cancer. Eur J Cancer 2005;41(16):2438-48
119. Sankpal UT, Goodison S, Abdelrahim M, et al. Targeting Sp1 transcription factors in prostate cancer therapy. Med Chem 2011;7(5):518-25
120. Ishibashi H, Nakagawa K, Onimaru M, et al. Sp1 decoy transfected to carcinoma cells suppresses the expression of vascular endothelial growth factor, transforming growth factor beta(1), and tissue factor and also cell growth and invasion activities. Cancer Res 2000;60(22):6531-6
121. Loeffler S, Fayard B, Weis J, et al. Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1. Int J Cancer 2005;115(2):202-13
122. Pore N, Liu S, Shu HK, et al. Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism. Mol Biol Cell 2004;15(11):4841-53
123. Eisermann K, Broderick CJ, Bazarov A, et al. Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site. Mol Cancer 2013;12(1):7
124. Malek A, Nunez LE, Magistri M, et al. Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer. PLoS One 2012;7(4):e35130
125. Hsieh AC, Ruggero D. Targeting eukaryotic translation initiation factor 4E (eIF4E) in cancer. Clin Cancer Res 2010;16(20):4914-20
126. Mamane Y, Petroulakis E, Rong LW, et al. eIF4E-from translation to transformation. Oncogene 2004;23(18):3172-9
127. Furic L, Rong L, Larsson O, et al. eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc Natl Acad Sci USA 2010;107(32):14134-9
128. Graff JR, Konicek BW, Lynch RL, et al. eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival. Cancer Res 2009;69(9):3866-73
129. Andrieu C, Taieb D, Baylot V, et al. Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E. Oncogene 2010;29(13):1883-96
130. Hayman TJ, Williams ES, Jamal M, et al. Translation initiation factor eIF4E is a target for tumor cell radiosensitization. Cancer Res 2012;72(9):2362-72
131. Ouyang X, Jessen WJ, Al-Ahmadie H, et al. Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res 2008;68(7):2132-44
132. Kajanne R, Miettinen P, Tenhunen M, et al. Transcription factor AP-1 promotes growth and radioresistance in prostate cancer cells. Int J Oncol 2009;35(5):1175-82
133. Sato N, Sadar MD, Bruchovsky N, et al. Androgenic induction of prostate-specific antigen gene is repressed by proteinprotein interaction between the androgen receptor and AP-1/c-jun in the human prostate cancer cell line LNCaP. J Biol Chem 1997;272(28):17485-94
134. Edwards J, Krishna NS, Mukherjee R, et al. The role of c-Jun and c-Fos expression in androgen-independent prostate cancer. J Pathol 2004;204(2):153-8
135. Chen SY, Cai C, Fisher CJ, et al. c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation. Oncogene 2006;25(54):7212-23
136. Zerbini LF, Wang Y, Cho JY, et al. Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer. Cancer Res 2003;63(9):2206-15
137. Hutmacher DW. Biomaterials offer cancer research the third dimension. Nat Mater 2010;9(2):90-3
138. Wang R, Xu J, Juliette L, et al. Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone. Semin Cancer Biol 2005;15(5):353-64