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Vol. 81, No. 2, 2008
Issue release date: August 2008
Urol Int 2008;81:228–233

Relationship between Glucocorticoid Receptor Signal Pathway and Androgen-Independent Prostate Cancer

Yan T.-Z. · Jin F.-S. · Xie L.-P. · Li L.-C.
aDepartment of Urology, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, and bDepartment of Urology, Affiliated Daping Hospital, Third Military Medical University, Chongqing, PR China; cDepartment of Urology, University of California San Francisco, and Veteran Affairs Medical Center San Francisco, San Francisco, Calif., USA

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Objective: To study the role of the glucocorticoid receptor (GR) signal pathway and downstream cytokine interleukin-6 (IL-6) in androgen-independent growth of prostate cancer (PC). Methods: The human androgen-dependent PC (ADPC) cell line LNCaP and androgen-independent PC (AIPC) cell line DU145 were cultured in vitro. Immunocytochemistry was used to examine the expression of the androgen receptor (AR), GR, HSP90 and IL-6. The GR antagonist RU486 was used to treat cultured cells, and the effects of RU486 on the proliferation of both cell lines were analyzed by MTT assay. Expression of HSP90 and IL-6 mRNA and protein was assessed by RT-PCR and Western blots, respectively. Results: LNCaP cells were AR-positive and GR-negative, whereas DU145 cells were GR-positive and AR-negative. The expression of HSP90 and IL-6 in DU145 cells were significantly stronger than that in LNCaP cells (p < 0.01). RU486 had no obvious effects on the growth of LNCaP cells, but exerted a significant time- and dose-dependent growth inhibition on DU145 cells at doses as low as 0.1 µmol/l. RU486 treatment of DU145 cells also resulted in a dose-dependent decrease in the expression of HSP90 and IL-6 mRNA and protein. Conclusions: The GR signal pathway may be the main survival pathway for DU145 cells. Abnormal hyperactivation of the GR signal pathway and its promoting the expression of HSP90 and IL-6 contribute to the progression of ADPC to AIPC after androgen ablation.

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  1. Suzuki H, Sato N, Watabe Y, Masai M, Seino S, Shimazaki J: Androgen receptor gene mutations in human prostate cancer. J Steroid Biochem Mol Biol 1993;46:759–765.
  2. Ruizeveld de Winter JA, Janssen PJ, Sleddens HM, Verleun-Mooijman MC, Trapman J, Brinkmann AO, Santerse AB, Schroder FH, van der Kwast TH: Androgen receptor status in localized and locally progressive hormone refractory human prostate cancer. Am J Pathol 1994;144:735–746.
  3. Zhang J, Thomas TZ, Kasper S, Matusik RJ: A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo. Endocrinology 2000;141:4698–4710.
  4. Culig Z, Bartsch G, Hobisch A: Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Molecular 2002;197:231–238.
  5. Smith PC, Hobisch A, Lin DL, Culig Z, Keller ET: Interleukin-6 and prostate cancer progression. Cytokine Growth Factor Rev 2001;12:33–40.
  6. Berns EM, de Boer W, Mulder E: Androgen-dependent growth regulation of and release of specific protein(s) by the androgen receptor containing human prostate tumor cell line LNCaP. Prostate 1986;9:247–259.
  7. Brolin J, Skoog L, Ekman P: Immunohistochemistry and biochemistry in detection of androgen, progesterone, and estrogen receptors in benign and malignant human prostatic tissue. Prostate 1992;20:281–295.
  8. Alen P, Claessens F, Schoenmakers E, Swinnen JV, Verhoeven G, Rombauts W, Peeters B: Interaction of the putative androgen receptor-specific coactivator ARA70/ELE1alpha with multiple steroid receptors and identification of an internally deleted ELE1beta isoform. Mol Endocrinol 1999;13:117–128.
  9. Mohler JL, Chen Y, Hamil K, Hall SH, Cidlowski JA, Wilson EM, French FS, Sar M: Androgen and glucocorticoid receptors in the stroma and epithelium of prostatic hyperplasia and carcinoma. Clin Cancer Res 1996;2:889–895.
  10. Nishimura K, Nonomura N, Satoh E, Harada Y, Nakayama M, Tokizane T, Fukui T, Ono Y, Inoue H, Shin M, Tsujimoto Y, Takayama H, Aozasa K, Okuyama A: Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst 2001;93:1739–1746.
  11. Davies P, Rushmere NK: Association of glucocorticoid receptors with prostate nuclear sites for androgen receptors and with androgen response elements. J Mol Endocrinol 1990;5:117–127.
  12. Cleutjens CB, Steketee K, van Eekelen CC, van der Korput JA, Brinkmann AO, Trapman J: Both androgen receptor and glucocorticoid receptor are able to induce prostate-specific antigen expression, but differ in their growth-stimulating properties of LNCaP cells. Endocrinology 1997;138:5293–5300.
  13. Jenkins BD, Pullen CB, Darimont BD: Novel glucocorticoid receptor coactivator effector mechanisms. Trends Endocrinol Metab 2001;12:122–126.
  14. Bone RC: Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med 1996;24:163–172.
  15. Drachenberg DE, Elgamal AA, Rowbotham R, Peterson M, Murphy GP: Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate 1999;41:127–133.
  16. Dondi D, Maggi R, Scaccianoce E, Martini L, Motta M, Poletti A: Expression and role of functional glucocorticoid receptors in the human androgen-independent prostate cancer cell line, DU145. J Mol Endocrinol 2001;26:185–191.
  17. Albrecht M, Janssen M, Konrad L, Renneberg H, Aumuller G: Effects of dexamethasone on proliferation of and fibronectin synthesis by human primary prostatic stromal cells in vitro. Andrologia 2002;34:11–21.
  18. Henning U, Krieger K, Loeffler S, Rivas F, Orozco G, de Castro MG, Rietschel M, Noethen MM, Klimke A: Increased levels of glucocorticoid receptors and enhanced glucocorticoid receptor auto-regulation after hydrocortisone challenge in B-lymphoblastoids from patients with affective disorders. Psychoneuroendocrinology 2005;30:325–332.
  19. Kumar R, Thompson EB: Gene regulation by the glucocorticoid receptor: structure: function relationship. J Steroid Biochem Mol Biol 2005;94:383–394.
  20. Vanaja DK, Mitchell SH, Toft DO, Young CY: Effect of geldanamycin on androgen receptor function and stability. Cell Stress Chaperones 2002;7:55–64.

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