Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2017, Article ID 9456020, 13 pages
https://doi.org/10.1155/2017/9456020
Review Article

Crosstalk between the Androgen Receptor and PPAR Gamma Signaling Pathways in the Prostate

Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA

Correspondence should be addressed to LaMonica V. Stewart; ude.cmm@trawetsl

Received 26 May 2017; Revised 29 August 2017; Accepted 14 September 2017; Published 18 October 2017

Academic Editor: Stéphane Mandard

Copyright © 2017 Emuejevoke Olokpa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. W. Watt, P. J. Lee, T. M'Timkulu, W. P. Chan, and R. Loor, “Human prostate-specific antigen: structural and functional similarity with serine proteases.,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 83, no. 10, pp. 3166–3170, 1986. View at Publisher · View at Google Scholar
  2. M. Wang, L. Valenzuela, G. Murphy, and T. Chu, “Purification of a human prostate specific antigen,” Investigative Urology, vol. 17, no. 2, pp. 159–163, 1979. View at Google Scholar
  3. H. Lilja, J. Oldbring, G. Rannevik, and C. B. Laurell, “Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen.,” The Journal of Clinical Investigation, vol. 80, no. 2, pp. 281–285, 1987. View at Publisher · View at Google Scholar · View at Scopus
  4. A.C. Society, “Cancer facts & figures,” 2017, vol., 2017.
  5. E. Castro and R. Eeles, “The role of BRCA1 and BRCA2 in prostate cancer,” Asian Journal of Andrology, vol. 14, no. 3, pp. 409–414, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Ryan, M. A. Jenkins, and A. K. Win, “Risk of prostate cancer in lynch syndrome: A systematic review and meta-Analysis,” Cancer Epidemiology, Biomarkers & Prevention, vol. 23, no. 3, pp. 437–449, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Cao and E. Giovannucci, “Obesity and prostate cancer,” Recent Results in Cancer Research, vol. 208, pp. 137–153, 2016. View at Publisher · View at Google Scholar · View at Scopus
  8. A. C. Vidal, L. E. Howard, D. M. Moreira, R. Castro-Santamaria, G. L. Andriole, and S. J. Freedland, “Obesity increases the risk for high-grade prostate cancer: Results from the REDUCE study,” Cancer Epidemiology, Biomarkers & Prevention, vol. 23, no. 12, pp. 2936–2942, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. V. J. Wu, D. Pang, W. W. Tang, X. Zhang, L. Li, and Z. You, “Obesity, age, ethnicity, and clinical features of prostate cancer patients,” American Journal of Clinical and Experimental Urology, vol. 5, no. 1, pp. 1–9, 2017. View at Publisher · View at Google Scholar
  10. N.C.C. Network, “Nccn clinical practice guidelines in oncololgy: Prostate cancer (version 2.2017),” 2017, https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
  11. P. E. Lonergan and D. J. Tindall, “Androgen receptor signaling in prostate cancer development and progression,” Journal of Carcinogenesis, vol. 10, article 20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. W. Wahli and E. Martinez, “Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression,” The FASEB Journal, vol. 5, no. 9, pp. 2243–2249, 1991. View at Google Scholar · View at Scopus
  13. C. S. Chang, J. Kokontis, and S. Liao, “Molecular cloning of human and rat complementary DNA encoding androgen receptors,” Science, vol. 240, no. 4850, pp. 324–326, 1988. View at Publisher · View at Google Scholar · View at Scopus
  14. D. B. Lubahn, D. R. Joseph, P. M. Sullivan, H. F. Willard, F. S. French, and E. M. Wilson, “Cloning of human androgen receptor complementary DNA and localization to the X chromosome,” Science, vol. 240, no. 4850, pp. 327–330, 1988. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Liao, J. Kokontis, T. Sai, and R. A. Hiipakka, “Androgen receptors: Structures, mutations, antibodies and cellular dynamics,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 34, no. 1-6, pp. 41–51, 1989. View at Publisher · View at Google Scholar · View at Scopus
  16. D. F. Smith and D. O. Toft, “Steroid receptors and their associated proteins,” Molecular Endocrinology, vol. 7, no. 1, pp. 4–11, 1993. View at Publisher · View at Google Scholar · View at Scopus
  17. V. Georget, J. M. Lobaccaro, B. Terouanne, P. Mangeat, J.-C. Nicolas, and C. Sultan, “Trafficking of the androgen receptor in living cells with fused green fluorescent protein-androgen receptor,” Molecular and Cellular Endocrinology, vol. 129, no. 1, pp. 17–26, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. R. K. Tyagi, Y. Lavrovsky, S. C. Ahn, C. S. Song, B. Chatterjee, and A. K. Roy, “Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells,” Molecular Endocrinology, vol. 14, no. 8, pp. 1162–1174, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. J. A. Ruizeveld De Winter, J. Trapman, M. Vermey, E. Mulder, N. D. Zegers, and T. H. Van der Kwast, “Androgen receptor expression in human tissues: An immunohistochemical study,” Journal of Histochemistry & Cytochemistry, vol. 39, no. 7, pp. 927–936, 1991. View at Publisher · View at Google Scholar · View at Scopus
  20. J. A. Tuxhorn, G. E. Ayala, and D. R. Rowley, “Reactive stroma in prostate cancer progression,” The Journal of Urology, vol. 166, no. 6, pp. 2472–2483, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Hayward, M. Rosen, and G. Cunha, “Stromal-epithelial interactions in the normal and neoplastic prostate,” British Journal of Urology, vol. 79, no. S2, pp. 18–26, 1997. View at Publisher · View at Google Scholar
  22. G. R. Cunha, S. W. Hayward, Y. Z. Wang, and W. A. Ricke, “Role of the stromal microenvironment in carcinogenesis of the prostate,” International Journal of Cancer, vol. 107, no. 1, pp. 1–10, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. G. R. Cunha, “Role of mesenchymal‐epithelial interactions in normal and abnormal development of the mammary gland and prostate,” Cancer, vol. 74, no. 3 S, pp. 1030–1044, 1994. View at Publisher · View at Google Scholar · View at Scopus
  24. S. W. Hayward and G. R. Cunha, “The prostate: Development and physiology,” Radiologic Clinics of North America, vol. 38, no. 1, pp. 1–14, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. A. I. Evangelou, S. F. Winter, W. J. Huss, R. A. Bok, and N. M. Greenberg, “Steroid hormones, polypeptide growth factors, hormone refractory prostate cancer, and the neuroendocrine phenotype,” Journal of Cellular Biochemistry, vol. 91, no. 4, pp. 671–683, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Wang, S. W. Hayward, M. Cao, K. A. Thayer, and G. R. Cunha, “Cell differentiation lineage in the prostate,” Differentiation, vol. 68, no. 4-5, pp. 270–279, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. G. R. Cunha and B. Lung, “The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild‐type and androgen‐insensitive (Tfm) Mice,” Journal of Experimental Zoology, vol. 205, no. 2, pp. 181–193, 1978. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Yu, C. Zhang, C.-C. Lin et al., “Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells,” The Prostate, vol. 71, no. 5, pp. 517–524, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Yu, C.-R. Yeh, Y. Niu et al., “Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts,” The Prostate, vol. 72, no. 4, pp. 437–449, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Bonkhoff and K. Remberger, “Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate,” Virchows Archiv A Pathological Anatomy and Histopathology, vol. 422, no. 1, pp. 35–38, 1993. View at Publisher · View at Google Scholar · View at Scopus
  31. G. S. Prins, L. Birch, and G. L. Greene, “Androgen receptor localization in different cell types of the adult rat prostate,” Endocrinology, vol. 129, no. 6, pp. 3187–3199, 1991. View at Publisher · View at Google Scholar · View at Scopus
  32. G. S. Evans and J. A. Chandler, “Cell proliferation studies in rat prostate I. the proliferative role of basal and secretory epithelial cells during normal growth,” The Prostate, vol. 10, no. 2, pp. 163–178, 1987. View at Publisher · View at Google Scholar · View at Scopus
  33. G. R. Cunha, R. M. Bigsby, P. S. Cooke, and Y. Sugimura, “Stromal-epithelial interactions in adult organs,” Cell Differentiation, vol. 17, no. 3, pp. 137–148, 1985. View at Publisher · View at Google Scholar · View at Scopus
  34. A. A. Donjacour and G. R. Cunha, “The effect of androgen deprivation on branching morphogenesis in the mouse prostate,” Developmental Biology, vol. 128, no. 1, pp. 1–14, 1988. View at Publisher · View at Google Scholar · View at Scopus
  35. B. Kwabi-Addo, M. Ozen, and M. Ittmann, “The role of fibroblast growth factors and their receptors in prostate cancer,” Endocrine-Related Cancer, vol. 11, no. 4, pp. 709–724, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. A. C. Levine, X.-H. Liu, P. D. Greenberg et al., “Androgens induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts,” Endocrinology, vol. 139, no. 11, pp. 4672–4678, 1998. View at Publisher · View at Google Scholar · View at Scopus
  37. K.-P. Lai, S. Yamashita, S. Vitkus, C.-R. Shyr, S. Yeh, and C. Chang, “Suppressed prostate epithelial development with impaired branching morphogenesis in mice lacking stromal fibromuscular androgen receptor,” Molecular Endocrinology, vol. 26, no. 1, pp. 52–66, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. J. T. Arnold and J. T. Isaacs, “Mechanisms involved in the progression of androgen-independent prostate cancers: It is not only the cancer cell's fault,” Endocrine-Related Cancer, vol. 9, no. 1, pp. 61–73, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Wong and Y. Wang, “Growth factors and epithelial-stromal interactions in prostate cancer development,” vol. 199 of International Review of Cytology, pp. 65–116, Elsevier, 2000. View at Publisher · View at Google Scholar
  40. N. Ohlson, A. Bergh, P. Stattin, and P. Wikström, “Castration-induced epithelial cell death in human prostate tissue is related to locally reduced IGF-1 levels,” The Prostate, vol. 67, no. 1, pp. 32–40, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. S. W. Hayward, Y. K. Hom, G. D. Grossfeld et al., “Malignant transformation in a nontumorigenic human prostatic epithelial cell line,” Cancer Research, vol. 61, no. 22, pp. 8135–8142, 2001. View at Google Scholar · View at Scopus
  42. E. A. Ricke, K. Williams, Y.-F. Lee et al., “Androgen hormone action in prostatic carcinogenesis: Stromal androgen receptors mediate prostate cancer progression, malignant transformation and metastasis,” Carcinogenesis, vol. 33, no. 7, pp. 1391–1398, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. D. A. Leach and G. Buchanan, “Stromal androgen receptor in prostate cancer development and progression,” Cancers, vol. 9, no. 1, article 10, 2017. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Lapouge, E. Erdmann, G. Marcias et al., “Unexpected paracrine action of prostate cancer cells harboring a new class of androgen receptor mutation - A new paradigm for cooperation among prostate tumor cells,” International Journal of Cancer, vol. 121, no. 6, pp. 1238–1244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. S. M. Dehm and D. J. Tindall, “Alternatively spliced androgen receptor variants,” Endocrine-Related Cancer, vol. 18, no. 5, pp. R183–R196, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. K. M. Wadosky and S. Koochekpour, “Androgen receptor splice variants and prostate cancer: From bench to bedside,” Oncotarget , vol. 8, no. 11, pp. 18550–18576, 2017. View at Publisher · View at Google Scholar · View at Scopus
  47. K. E. Ware, M. A. Garcia-Blanco, A. J. Armstrong, and S. M. Dehm, “Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer,” Endocrine-Related Cancer, vol. 21, no. 4, pp. T87–T103, 2014. View at Publisher · View at Google Scholar · View at Scopus
  48. S. M. Dehm, L. J. Schmidt, H. V. Heemers, R. L. Vessella, and D. J. Tindall, “Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance,” Cancer Research, vol. 68, no. 13, pp. 5469–5477, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Marcias, E. Erdmann, G. Lapouge et al., “Identification of novel truncated Androgen Receptor (AR) mutants including unreported pre-mRNA splicing variants in the 22Rv1 hormone-refractory Prostate Cancer (PCa) cell line,” Human Mutation, vol. 31, no. 1, pp. 74–80, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. Z. Guo, X. Yang, F. Sun et al., “A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth,” Cancer Research, vol. 69, no. 6, pp. 2305–2313, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Hu, W. B. Isaacs, and J. Luo, “A snapshot of the expression signature of androgen receptor splicing variants and their distinctive transcriptional activities,” The Prostate, vol. 71, no. 15, pp. 1656–1667, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. P. A. Watson, Y. F. Chen, M. D. Balbas et al., “Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 107, no. 39, pp. 16759–16765, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Hu, T. A. Dunn, S. Wei et al., “Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer,” Cancer Research, vol. 69, no. 1, pp. 16–22, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. E. Hörnberg, E. B. Ylitalo, S. Crnalic et al., “Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival,” PLoS ONE, vol. 6, no. 4, Article ID e19059, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. E. S. Antonarakis, C. Lu, B. Luber et al., “Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer,” JAMA Oncology, vol. 1, no. 5, pp. 582–591, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. E. S. Antonarakis, C. Lu, B. Luber, H. Wang, Y. Chen, Y. Zhu et al., “Clinical significance of androgen receptor splice variant-7 mrna detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line abiraterone and enzalutamide,” Journal of Clinical Oncology, vol. 35, no. 19, pp. 2149–2156, 2017. View at Google Scholar
  57. M. Kohli, Y. Ho, D. W. Hillman et al., “Androgen receptor variant AR-V9 is coexpressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance,” Clinical Cancer Research, vol. 23, no. 16, pp. 4704–4715, 2017. View at Publisher · View at Google Scholar
  58. D. Xu, Y. Zhan, Y. Qi et al., “Androgen receptor splice variants dimerize to transactivate target genes,” Cancer Research, vol. 75, no. 17, pp. 3663–3671, 2015. View at Publisher · View at Google Scholar · View at Scopus
  59. B. J. Feldman and D. Feldman, “The development of androgen-independent prostate cancer,” Nature Reviews Cancer, vol. 1, no. 1, pp. 34–45, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Sun, C. C. T. Sprenger, R. L. Vessella et al., “Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant,” The Journal of Clinical Investigation, vol. 120, no. 8, pp. 2715–2730, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Huggins and C. V. Hodges, “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.,” The Journal of Urology, vol. 168, no. 1, pp. 9–12, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. K. L. Lee and D. M. Peehl, “Molecular and cellular pathogenesis of benign prostatic hyperplasia,” The Journal of Urology, vol. 172, no. 5 I, pp. 1784–1791, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. R. J. Santen, “Clinical review 37: Endocrine treatment of prostate cancer,” The Journal of Clinical Endocrinology & Metabolism, vol. 75, no. 3, pp. 685–689, 1992. View at Publisher · View at Google Scholar · View at Scopus
  64. K. E. Knudsen and T. M. Penning, “Partners in crime: Deregulation of AR activity and androgen synthesis in prostate cancer,” Trends in Endocrinology & Metabolism, vol. 21, no. 5, pp. 315–324, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. K. E. Knudsen and H. I. Scher, “Starving the addiction: New opportunities for durable suppression of AR signaling in prostate cancer,” Clinical Cancer Research, vol. 15, no. 15, pp. 4792–4798, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. K. R. Lamont and D. J. Tindall, “Minireview: Alternative activation pathways for the androgen receptor in prostate cancer,” Molecular Endocrinology, vol. 25, no. 6, pp. 897–907, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Ho and S. M. Dehm, “Androgen receptor rearrangement and splicing variants in resistance to endocrine therapies in prostate cancer,” Endocrinology, vol. 158, no. 6, pp. 1533–1542, 2017. View at Publisher · View at Google Scholar
  68. E. McCrea, T. M. Sissung, D. K. Price, C. H. Chau, and W. D. Figg, “Androgen receptor variation affects prostate cancer progression and drug resistance,” Pharmacological Research, vol. 114, pp. 152–162, 2016. View at Publisher · View at Google Scholar · View at Scopus
  69. K. Dalal, M. Roshan-Moniri, A. Sharma et al., “Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer,” The Journal of Biological Chemistry, vol. 289, no. 38, pp. 26417–26429, 2014. View at Google Scholar
  70. P. Tontonoz and B. M. Spiegelman, “Fat and beyond: the diverse biology of PPARγ,” Annual Review of Biochemistry, vol. 77, pp. 289–312, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Jiang, S. B. Shappell, and S. W. Hayward, “Approaches to understanding the importance and clinical implications of peroxisome proliferator-activated receptor gamma (PPARγ) signaling in prostate cancer,” Journal of Cellular Biochemistry, vol. 91, no. 3, pp. 513–527, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Diezko and G. Suske, “Ligand binding reduces sumoylation of the peroxisome proliferator-activated receptor γ (PPARγ) activation function 1 (AF1) domain,” PLoS ONE, vol. 8, no. 6, Article ID e66947, 2013. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Ohshima, H. Koga, and K. Shimotahno, “Transcriptional activity of peroxisome proliferator-activated receptor γ is modulated by SUMO-1 modification,” The Journal of Biological Chemistry, vol. 279, no. 28, pp. 29551–29557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. G. Pascual, A. L. Fong, S. Ogawa et al., “A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ,” Nature, vol. 437, no. 7059, pp. 759–763, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. L. Grøntved, M. S. Madsen, M. Boergesen, R. G. Roeder, and S. Mandrup, “MED14 tethers mediator to the N-terminal domain of peroxisome proliferator-activated receptor γ and is required for full transcriptional activity and adipogenesis,” Molecular and Cellular Biology, vol. 30, no. 9, pp. 2155–2169, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. L. Fajas, D. Auboeuf, E. Raspé et al., “The organization, promoter analysis, and expression of the human PPARγ gene,” The Journal of Biological Chemistry, vol. 272, no. 30, pp. 18779–18789, 1997. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Meirhaeghe, L. Fajas, F. Gouilleux et al., “A functional polymorphism in a STAT5B site of the human PPARγ3 gene promoter affects height and lipid metabolism in a French population,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 2, pp. 289–294, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. C. L. Chaffer, D. M. Thomas, E. W. Thompson, and E. D. Williams, “PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma,” BMC Cancer, vol. 6, article 53, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. V. Subbarayan, A. L. Sabichi, J. Kim et al., “Differential peroxisome proliferator-activated receptor-γ isoform expression and agonist effects in normal and malignant prostate cells,” Cancer Epidemiology, Biomarkers & Prevention, vol. 13, no. 11, pp. 1710–1716, 2004. View at Google Scholar · View at Scopus
  80. M. Jiang, S. Fernandez, W. G. Jerome et al., “Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy,” Cell Death & Differentiation, vol. 17, no. 3, pp. 469–481, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. I. Ahmad, E. Mui, L. Galbraith et al., “Sleeping beauty screen reveals Pparg activation in metastatic prostate cancer,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 113, no. 29, pp. 8290–8295, 2016. View at Publisher · View at Google Scholar · View at Scopus
  82. E. Mueller, M. Smith, P. Sarraf et al., “Effects of ligand activation of peroxisome proliferator-activated receptor γ in human prostate cancer,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 97, no. 20, pp. 10990–10995, 2000. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. Segawa, R. Yoshimura, T. Hase et al., “Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer,” The Prostate, vol. 51, no. 2, pp. 108–116, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. P. E. Moss, B. E. Lyles, and L. V. Stewart, “The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells,” Experimental Cell Research, vol. 316, no. 20, pp. 3478–3488, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. L. C. Hsi, L. C. Wilson, and T. E. Eling, “Opposing effects of 15-lipoxygenase-1 and -2 metabolites on MAPK signaling in prostate: Alteration in peroxisome proliferator-activated receptor γ,” The Journal of Biological Chemistry, vol. 277, no. 43, pp. 40549–40556, 2002. View at Publisher · View at Google Scholar · View at Scopus
  86. S. B. Shappell, R. A. Gupta, S. Manning et al., “15S-hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor γ and inhibits proliferation in PC3 prostate carcinoma cells,” Cancer Research, vol. 61, no. 2, pp. 497–503, 2001. View at Google Scholar · View at Scopus
  87. S. Tang, B. Bhatia, C. J. Maldonado et al., “Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells,” The Journal of Biological Chemistry, vol. 277, no. 18, pp. 16189–16201, 2002. View at Publisher · View at Google Scholar · View at Scopus
  88. T. O. Akinyeke and L. V. Stewart, “Troglitazone suppresses c-Myc levels in human prostate cancer cells via a PPARγ-independent mechanism,” Cancer Biology & Therapy, vol. 11, no. 12, pp. 1046–1058, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Kubota, K. Koshizuka, E. A. Williamson et al., “Ligand for peroxisome proliferator-activated receptor gamma (Troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo,” Cancer Research, vol. 58, no. 15, pp. 3344–3352, 1998. View at Google Scholar · View at Scopus
  90. B. E. Lyles, T. O. Akinyeke, P. E. Moss, and L. V. Stewart, “Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARγ-dependent and PPARγ-independent pathways,” Cell Cycle, vol. 8, no. 2, pp. 268–277, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Panigrahy, S. Singer, L. Q. Shen et al., “PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis,” The Journal of Clinical Investigation, vol. 110, no. 7, pp. 923–932, 2002. View at Publisher · View at Google Scholar · View at Scopus
  92. Y. Xu, S. Iyengar, R. L. Roberts, S. B. Shappell, and D. M. Peehl, “Primary culture model of peroxisome proliferator-activated receptor γ activity in prostate cancer cells,” Journal of Cellular Physiology, vol. 196, no. 1, pp. 131–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Suzuki, Y. Mori, A. Nagano et al., “Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, suppresses rat prostate carcinogenesis,” International Journal of Molecular Sciences, vol. 17, no. 12, article 2071, 2016. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Wei, L.-F. Lin, C.-C. Yang et al., “Thiazolidinediones modulate the expression of β-catenin and other cell-cycle regulatory proteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor γ,” Molecular Pharmacology, vol. 72, no. 3, pp. 725–733, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Santha, G. Davaakhuu, A. Basu et al., “Modulation of glycogen synthase kinase-3β following TRAIL combinatorial treatment in cancer cells,” Oncotarget , vol. 7, no. 41, pp. 66892–66905, 2016. View at Publisher · View at Google Scholar · View at Scopus
  96. C. Wang, M. Fu, M. D'Amico, C. Albanese, J. N. Zhou, M. Brownlee et al., “Inhibition of cellular proliferation through ikappab kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin d1,” Molecular & Cellular Biology, vol. 21, no. 9, pp. 3057–3070, 2001. View at Publisher · View at Google Scholar
  97. F. Yin, S. Wakino, Z. Liu et al., “Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators,” Biochemical and Biophysical Research Communications, vol. 286, no. 5, pp. 916–922, 2001. View at Publisher · View at Google Scholar · View at Scopus
  98. C. Qin, R. Burghardt, R. Smith, M. Wormke, J. Stewart, and S. Safe, “Peroxisome proliferator-activated receptor γ agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor α in MCF-7 breast cancer cells,” Cancer Research, vol. 63, no. 5, pp. 958–964, 2003. View at Google Scholar · View at Scopus
  99. J.-W. Huang, C.-W. Shiau, and Y.-T. Yang, “Peroxisome proliferator-activated receptor γ-independent ablation of cyclin D1 by thiazolidinediones and their derivatives in breast cancer cells,” Molecular Pharmacology, vol. 67, no. 4, pp. 1342–1348, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Cerbone, C. Toaldo, S. Laurora et al., “4-Hydroxynonenal and PPARγ ligands affect proliferation, differentiation, and apoptosis in colon cancer cells,” Free Radical Biology & Medicine, vol. 42, no. 11, pp. 1661–1670, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. M. A. Lea, M. Sura, and C. Desbordes, “Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and antagonists,” Anticancer Reseach, vol. 24, no. 5, pp. 2765–2771, 2004. View at Google Scholar · View at Scopus
  102. A. Rossi, P. Kapahi, G. Natoli et al., “Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase,” Nature, vol. 403, no. 6765, pp. 103–108, 2000. View at Publisher · View at Google Scholar · View at Scopus
  103. D. W. Strand, M. Jiang, T. A. Murphy et al., “PPARγ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation,” Cell Death & Disease, vol. 3, no. 8, article e361, 2012. View at Publisher · View at Google Scholar · View at Scopus
  104. J. I. Hisatake, T. Ikezoe, M. Carey, S. Holden, S. Tomoyasu, and H. P. Koeffler, “Down-regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor γ in human prostate cancer,” Cancer Research, vol. 60, no. 19, pp. 5494–5498, 2000. View at Google Scholar · View at Scopus
  105. C.-C. Yang, C.-Y. Ku, S. Wei et al., “Peroxisome proliferator-activated receptor γ-independent repression of prostate-specific antigen expression by thiazolidinediones in prostate cancer cells,” Molecular Pharmacology, vol. 69, no. 5, pp. 1564–1570, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. C.-C. Yang, Y.-C. Wang, S. Wei et al., “Peroxisome proliferator-activated receptor γ-independent suppression of androgen receptor expression by troglitazone mechanism and pharmacologic exploitation,” Cancer Research, vol. 67, no. 7, pp. 3229–3238, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. D. Nagata, H. Yoshihiro, M. Nakanishi et al., “Peroxisome proliferator-activated receptor-γ and growth inhibition by its ligands in prostate cancer,” Cancer Epidemiology, vol. 32, no. 3, pp. 259–266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Kaikkonen, V. Paakinaho, P. Sutinen, A.-L. Levonen, and J. J. Palvimo, “Prostaglandin 15d-PGJ2 inhibits androgen receptor signaling in prostate cancer cells,” Molecular Endocrinology, vol. 27, no. 2, pp. 212–223, 2013. View at Publisher · View at Google Scholar · View at Scopus
  109. B. Y. Tew, T. B. Hong, M. Otto-Duessel et al., “Vitamin K epoxide reductase regulation of androgen receptor activity,” Oncotarget , vol. 8, no. 8, pp. 13818–13831, 2017. View at Publisher · View at Google Scholar · View at Scopus
  110. J. M. Seargent, E. A. Yates, and J. H. Gill, “GW9662, a potent antagonist of PPARγ, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARγ agonist rosiglitazone, independently of PPARγ activation,” British Journal of Pharmacology, vol. 143, no. 8, pp. 933–937, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. E. Olokpa, A. Bolden, and L. V. Stewart, “The Androgen Receptor Regulates PPARγ Expression and Activity in Human Prostate Cancer Cells,” Journal of Cellular Physiology, vol. 231, no. 12, pp. 2664–2672, 2016. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Singh, J. N. Artaza, W. E. Taylor et al., “Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with β-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors,” Endocrinology, vol. 147, no. 1, pp. 141–154, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. A.-M. Lefebvre, J. Peinado-Onsurbe, I. Leitersdorf et al., “Regulation of lipoprotein metabolism by thiazolidinediones occurs through a distinct but complementary mechanism relative to fibrates,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 9, pp. 1756–1764, 1997. View at Publisher · View at Google Scholar · View at Scopus
  114. N. Noy, E. Morgan, and P. Kannan-Thulasiraman, “Involvement of fatty acid binding protein 5 and PPAR β/δ in prostate cancer cell growth,” PPAR Research, Article ID 234629, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. M. L. De Santis, R. Hammamieh, R. Das, and M. Jett, “Adipocyte-fatty acid binding protein induces apoptosis in du145 prostate cancer cells,” Journal of Experimental Therapeutics and Oncology, vol. 4, no. 2, pp. 91–100, 2004. View at Google Scholar
  116. M. A. White, C. Lin, K. Rajapakshe et al., “Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer,” Molecular Cancer Research, vol. 15, no. 8, pp. 1017–1028, 2017. View at Publisher · View at Google Scholar
  117. C. E. Massie, A. Lynch, A. Ramos-Montoya et al., “The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis,” EMBO Journal, vol. 30, no. 13, pp. 2719–2733, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. P. Puigserver, Z. Wu, C. W. Park, R. Graves, M. Wright, and B. M. Spiegelman, “A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis,” Cell, vol. 92, no. 6, pp. 829–839, 1998. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Shiota, A. Yokomizo, Y. Tada et al., “Peroxisome proliferator-activated receptor γ coactivator-1α interacts with the androgen receptor (AR) and promotes prostate cancer cell growth by activating the AR,” Molecular Endocrinology, vol. 24, no. 1, pp. 114–127, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. J. B. Tennakoon, Y. Shi, J. J. Han et al., “Androgens regulate prostate cancer cell growth via an AMPK-PGC-1α-mediated metabolic switch,” Oncogene, vol. 33, no. 45, pp. 5251–5261, 2014. View at Publisher · View at Google Scholar · View at Scopus
  121. S. A. Oñate, S. Y. Tsai, M.-J. Tsai, and B. W. O'Malley, “Sequence and characterization of a coactivator for the steroid hormone receptor superfamily,” Science, vol. 270, no. 5240, pp. 1354–1357, 1995. View at Publisher · View at Google Scholar · View at Scopus
  122. J. J. Voegel, M. J. S. Heine, C. Zechel, P. Chambon, and H. Gronemeyer, “TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors,” EMBO Journal, vol. 15, no. 14, pp. 3667–3675, 1996. View at Google Scholar · View at Scopus
  123. V. V. Ogryzko, R. L. Schiltz, V. Russanova, B. H. Howard, and Y. Nakatani, “The transcriptional coactivators p300 and CBP are histone acetyltransferases,” Cell, vol. 87, no. 5, pp. 953–959, 1996. View at Publisher · View at Google Scholar · View at Scopus
  124. A. J. Bannister and T. Kouzarides, “The CBP co-activator is a histone acetyltransferase,” Nature, vol. 384, no. 6610, pp. 641–643, 1996. View at Publisher · View at Google Scholar · View at Scopus
  125. I. U. Agoulnik, A. Vaid, W. E. Bingman III et al., “Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression,” Cancer Research, vol. 65, no. 17, pp. 7959–7967, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. C. W. Gregory, B. He, R. T. Johnson et al., “A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy,” Cancer Research, vol. 61, no. 11, pp. 4315–4319, 2001. View at Google Scholar · View at Scopus
  127. K. E. Knudsen, W. K. Cavenee, and K. C. Arden, “D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability,” Cancer Research, vol. 59, no. 10, pp. 2297–2301, 1999. View at Google Scholar · View at Scopus
  128. C. E. Petre, Y. B. Wetherill, M. Danielsen, and K. E. Knudsen, “Cyclin D1: Mechanism and consequence of androgen receptor co-repressor activity,” The Journal of Biological Chemistry, vol. 277, no. 3, pp. 2207–2215, 2002. View at Publisher · View at Google Scholar · View at Scopus
  129. C. A. Berrevoets, A. Umar, J. Trapman, and A. O. Brinkmann, “Differential modulation of androgen receptor transcriptional activity by the nuclear receptor co-repressor (N-CoR),” Biochemical Journal, vol. 379, no. 3, pp. 731–738, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. M. C. Hodgson, I. Astapova, S. Cheng et al., “The androgen receptor recruits nuclear receptor corepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists,” The Journal of Biological Chemistry, vol. 280, no. 8, pp. 6511–6519, 2005. View at Publisher · View at Google Scholar · View at Scopus
  131. P. Li, W. Fan, J. Xu et al., “Adipocyte NCoR knockout decreases PPARγ phosphorylation and enhances PPARγ activity and insulin sensitivity,” Cell, vol. 147, no. 4, pp. 815–826, 2011. View at Publisher · View at Google Scholar · View at Scopus
  132. S. Battaglia, O. Maguire, J. L. Thorne et al., “Elevated NCOR1 disrupts PPARα/γ signaling in prostate cancer and forms a targetable epigenetic lesion,” Carcinogenesis, vol. 31, no. 9, pp. 1650–1660, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. S. Y. Kim, A. Y. Kim, H. W. Lee et al., “miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARγ expression,” Biochemical and Biophysical Research Communications, vol. 392, no. 3, pp. 323–328, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. J.-J. Lee, A. Drakaki, D. Iliopoulos, and K. Struhl, “MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells,” Oncogene, vol. 31, no. 33, pp. 3818–3825, 2012. View at Publisher · View at Google Scholar · View at Scopus
  135. E. K. Lee, M. J. Lee, K. Abdelmohsen et al., “miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor γ expression,” Molecular and Cellular Biology, vol. 31, no. 4, pp. 626–638, 2011. View at Publisher · View at Google Scholar · View at Scopus
  136. B.-C. Jeong, I.-H. Kang, and J.-T. Koh, “MicroRNA-302a inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ expression,” FEBS Letters, vol. 588, no. 18, pp. 3427–3434, 2014. View at Publisher · View at Google Scholar · View at Scopus
  137. X. Li, Y. Chen, S. Wu et al., “MicroRNA-34a and microRNA-34c promote the activation of human hepatic stellate cells by targeting peroxisome proliferator-activated receptor γ,” Molecular Medicine Reports, vol. 11, no. 2, pp. 1017–1024, 2015. View at Publisher · View at Google Scholar · View at Scopus
  138. C. E. Fletcher, D. A. Dart, A. Sita-lumsden, H. Cheng, P. S. Rennie, and C. L. Bevan, “Androgen-regulated processing of the oncomir MiR-27a, which targets Prohibitin in prostate cancer,” Human Molecular Genetics, vol. 21, no. 14, Article ID dds139, pp. 3112–3127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  139. P. Östling, S.-K. Leivonen, A. Aakula et al., “Systematic analysis of microRNAs targeting the androgen receptor in prostate cancer cells,” Cancer Research, vol. 71, no. 5, pp. 1956–1967, 2011. View at Publisher · View at Google Scholar · View at Scopus