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ABSTRACT Osteoprotegerin (OPG), a key regulator of bone resorption, is hypothesized to have a role in prostate cancer (CaP) bone metastasis. As advanced CaP is treated by androgen ablation,

we examined if androgen modulates OPG expression by CaP cell lines _in vitro_. Basal levels of secreted OPG protein were significantly greater in androgen-independent PC-3 cells compared

with androgen-responsive LNCaP-FGC cells (_P_<0.001); OPG was not detected in the androgen-responsive CaP cell lines LAPC-4 or DuCaP. Treatment with 5_α_-dihydrotestosterone (5_α_-DHT)

significantly decreased OPG protein levels in both PC-3 and LNCaP-FGC, with maximal suppression using 10−9–10−7 M 5_α_-DHT in PC-3 (_P_<0.01; day 3), and using 10−10–10−9 M 5_α_-DHT in

LNCaP-FGC cells (_P_<0.01; day 6). OPG messenger RNA levels were not significantly altered by this 5_α_-DHT treatment. Co-treatment with 10−6 M flutamide blocked 5_α_-DHT inhibition of

OPG protein expression in LNCaP-FGC cells. These data suggest that androgen may modulate OPG protein levels in CaP cells lines _in vitro_ using a post-transcriptional mechanism. Access

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ACTIVATION Article Open access 20 January 2022 REFERENCES * Carlin BI, Andriole GL . The natural history, skeletal complications, and management of bone metastases in patients with prostate

carcinoma. _Cancer_ 2000; 88: 2989–2994. Article  CAS  Google Scholar  * McMurtry CT, McMurtry JM . Metastatic prostate cancer: complications and treatment. _J Am Geriatr Soc_ 2003; 51:

1136–1142. Article  Google Scholar  * Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR, Kostenuik PJ . Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in

syngeneic and nude mouse models of experimental bone metastasis. _Cancer Res_ 2001; 61: 4432–4436. CAS  Google Scholar  * Penno H, Silfverswärd C-J, Frosta A, Brändström H, Nilsson O,

Ljunggren Ö . Osteoprotegerin secretion from prostate cancer is stimulated by cytokines, _in vitro_. _Biochem Biophys Res Commun_ 2002; 293: 451–455. Article  CAS  Google Scholar  * Pollen

JJ, Reznek RH, Talner LB . Lysis of osteoblastic lesions in prostatic cancer: a sign of progression. _AJR Am J Roentgenol_ 1984; 142: 1175–1179. Article  CAS  Google Scholar  * Zhang J, Dai

J, Qi Y, Lin DL, Smith P, Strayhorn C _et al_. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. _J Clin Invest_ 2001; 107:

1235–1244. Article  CAS  Google Scholar  * Balk SP . Androgen receptor as a target in androgen-independent prostate cancer. _Urology_ 2002; 60: 132–138. Article  Google Scholar  * Hara T,

Miyazaki J, Araki H, Yamaoka M, Kanzaki N, Kusaka M _et al_. Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. _Cancer Res_ 2003; 63: 149–153.

CAS  Google Scholar  * Orwoll ES, Klein RF . Osteoporosis in men. _Endocr Rev_ 1995; 16: 87–116. Article  CAS  Google Scholar  * Syed F, Khosla S . Mechanisms of sex steroid effects on bone.

_Biochem Biophys Res Commun_ 2005; 328: 688–696. Article  CAS  Google Scholar  * Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R _et al_. Osteoprotegerin: a novel secreted

protein involved in the regulation of bone density. _Cell_ 1997; 89: 309–319. Article  CAS  Google Scholar  * Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano N, Fujise K _et al_. Identity

of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis _in vitro_. _Endocrinology_ 1998; 139: 1329–1337. Article

  Google Scholar  * Lacey D, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T _et al_. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. _Cell_

1998; 93: 165–176. Article  CAS  Google Scholar  * Brown JM, Corey E, Lee ZD, True LD, Yun TJ, Tondravi M _et al_. Osteoprotegerin and RANK ligand expression in prostate cancer. _Urology_

2001; 57: 611–616. Article  CAS  Google Scholar  * Brown JM, Vessella RL, Kostenuik PJ, Dunstan CR, Lange PH, Corey E . Serum osteoprotegerin levels are increased in patients with advanced

prostate cancer. _Clin Cancer Res_ 2001; 7: 2977–2983. CAS  Google Scholar  * Jung K, Lein M, von Hösslin K, Brux B, Schnorr D, Loening SA _et al_. Osteoprotegerin in serum as a novel marker

of bone metastatic spread in prostate cancer. _Clin Chem_ 2001; 47: 2061–2063. CAS  Google Scholar  * Jung K, Stephan C, Semjonow A, Lein M, Schnorr D, Loening SA . Serum osteoprotegerin

and receptor activator of nuclear factor-_κ_B ligand as indicators of disturbed osteoclastogenesis in patients with prostate cancer. _J Urol_ 2003; 170: 2302–2305. Article  Google Scholar  *

Eaton CL, Wells JM, Holen I, Croucher PI, Hamdy FC . Serum osteoprotegerin (OPG) levels are associated with disease progression and response to androgen ablation in patients with prostate

cancer. _Prostate_ 2004; 59: 304–310. Article  CAS  Google Scholar  * Holen I, Croucher PI, Hamdy FC, Eaton CL . Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells.

_Cancer Res_ 2002; 62: 1619–1623. CAS  Google Scholar  * Hofbauer LC, Hicok KC, Chen D, Khosla S . Regulation of osteoprotegerin production by androgens and anti-androgens in human

osteoblastic lineage cells. _Eur J Endocrinol_ 2002; 147: 269–273. Article  CAS  Google Scholar  * Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS . Phenol red in tissue culture media

is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. _Proc Natl Acad Sci USA_ 1986; 83: 2496–2500. Article  CAS  Google Scholar  * Buchanan G, Craft

PS, Yang M, Cheong A, Prescott J, Jia L _et al_. PC-3 cells with enhanced androgen receptor signaling: a model for clonal selection in prostate cancer. _Prostate_ 2004; 60: 352–366. Article

  CAS  Google Scholar  * Marreiros A, Czolij R, Yardley G, Crossley M, Jackson P . Identification of regulatory regions within the KAI1 promoter: a role for binding of AP1, AP2 and p53.

_Gene_ 2003; 302: 155–164. Article  CAS  Google Scholar  * Tilley WD, Bentel JM, Aspinall JO, Hall RE, Horsfall DJ . Evidence for a novel mechanism of androgen resistance in the human

prostate cancer cell line, PC-3. _Steroids_ 1995; 60: 180–186. Article  CAS  Google Scholar  * Lin MF, Meng TC, Rao PC, Chang C, Schönthal AH, Lin FF . Expression of human prostatic acid

phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines. _J Biol Chem_ 1998; 273: 5939–5947. Article  CAS  Google Scholar  * Alimirah F, Chen J,

Basrawala Z, Xin H, Choubey D . DU-145 and PC-3 human prostate cancer cell lines express androgen receptor: implications for the androgen receptor functions and regulation. _FEBS Lett_ 2006;

580: 2294–2300. Article  CAS  Google Scholar  * Yuan S, Trachtenberg J, Mills GB, Brown TJ, Xu F, Keating A . Androgen-induced inhibition of cell proliferation in an androgen-insensitive

prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA. _Cancer Res_ 1993; 53: 1304–1311. CAS  Google Scholar  * Garcia-Arenas R, Lin F-F, Lin D, Jin

LP, Shih CC, Chang C _et al_. The expression of prostatic acid phosphatase is transcriptionally regulated in human prostate carcinoma cells. _Mol Cell Endocrinol_ 1995; 111: 29–37. Article 

CAS  Google Scholar  * Benten WP, Lieberherr M, Sekeris CE, Wunderlich F . Testosterone induces Ca2+ influx via non-genomic surface receptors in activated T cells. _FEBS Lett_ 1997; 407:

211–214. Article  CAS  Google Scholar  * Wehling M . Specific, nongenomic actions of steroid hormones. _Annu Rev Physiol_ 1997; 59: 365–393. Article  CAS  Google Scholar  * Nadal A, Rovira

JM, Laribi O, Leon-quinto T, Andreu E, Ripoll C _et al_. Rapid insulinotropic effect of 17_β_-estradiol via a plasma membrane receptor. _FASEB J_ 1998; 12: 1341–1348. Article  CAS  Google

Scholar  * Benten WP, Lieberherr M, Stamm O, Wrehlke C, Guo Z, Wunderlich F . Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. _Mol Biol

Cell_ 1999; 10: 3113–3123. Article  CAS  Google Scholar  * Lyng FM, Jones GR, Rommerts FF . Rapid androgen actions on calcium signaling in rat sertoli cells and two human prostatic cell

lines: similar biphasic responses between 1 picomolar and 100 nanomolar concentrations. _Biol Reprod_ 2000; 63: 736–747. Article  CAS  Google Scholar  * Papakonstanti EA, Kampa M, Castanas

E, Stournaras C . A rapid, nongenomic, signaling pathway regulates the actin reorganization induced by activation of membrane testosterone receptors. _Mol Endocrinol_ 2003; 17: 870–881.

Article  CAS  Google Scholar  * Steinsapir J, Socci R, Reinach P . Effects of androgen on intracellular calcium of LNCaP cells. _Biochem Biophys Res Commun_ 1991; 179: 90–96. Article  CAS 

Google Scholar  * Kampa M, Papakonstanti EA, Alexaki VI, Hatzoglou A, Stournaras C, Castanas E . The opioid agonist ethylketocyclazocine reverts the rapid, non-genomic effects of membrane

testosterone receptors in the human prostate LNCaP cell line. _Exp Cell Res_ 2004; 294: 434–445. Article  CAS  Google Scholar  * Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H,

Dalrymple S _et al_. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. _J Clin Invest_ 1995; 95: 2886–2895. Article  CAS  Google

Scholar  * Hofbauer LC, Khosla S . Androgen effects on bone metabolism: recent progress and controversies. _Eur J Endocrinol_ 1999; 140: 271–286. Article  CAS  Google Scholar  * Pederson L,

Kremer M, Judd J, Pascoe D, Spelsberg TC, Riggs BL _et al_. Androgens regulate bone resorption activity of isolated osteoclasts _in vitro_. _Proc Natl Acad Sci USA_ 1999; 96: 505–510.

Article  CAS  Google Scholar  * Gennari L, Nuti R, Bilezikian JP . Aromatase activity and bone homeostasis in men. _J Clin Endocrinol Metab_ 2004; 89: 5898–5907. Article  CAS  Google Scholar

  * Wittrant Y, Théoleyre S, Chipoy C, Padines M, Blanchard F, Heymann D _et al_. RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. _Biochim Biophys Acta_

2004; 1704: 49–57. CAS  Google Scholar  * Blair JM, Zhou H, Seibel MJ, Dunstan CR . Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. _Nat

Clin Pract Oncol_ 2006; 3: 41–49. Article  CAS  Google Scholar  * Grimaud E, Soubigou L, Couillaud S, Coipeau P, Moreau A, Passuti N _et al_. Receptor activator of nuclear factor _κ_B ligand

(RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. _Am J Pathol_ 2003; 163: 2021–2031. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Dr

Barbara Szymanska and Elizabeth Kingsley for their excellent technical assistance. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Oncology Research Centre, Prince of Wales Hospital, Randwick,

New South Wales, Australia K Vandyke, P Jackson, A Rowe, P J Russell & J M Blair * Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia K Vandyke, 

P Jackson, A Rowe, P J Russell & J M Blair * School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia K Vandyke Authors *

K Vandyke View author publications You can also search for this author inPubMed Google Scholar * P Jackson View author publications You can also search for this author inPubMed Google

Scholar * A Rowe View author publications You can also search for this author inPubMed Google Scholar * P J Russell View author publications You can also search for this author inPubMed 

Google Scholar * J M Blair View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to J M Blair. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Vandyke, K., Jackson, P., Rowe, A. _et al._ Androgen decreases osteoprotegerin expression in prostate cancer cells. _Prostate

Cancer Prostatic Dis_ 10, 160–166 (2007). https://doi.org/10.1038/sj.pcan.4500927 Download citation * Received: 18 September 2006 * Accepted: 13 October 2006 * Published: 26 December 2006 *

Issue Date: 01 May 2007 * DOI: https://doi.org/10.1038/sj.pcan.4500927 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link

Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * osteoprotegerin *

androgen * bone metastasis * bone resorption