Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy

Endocrine-Related Cancer

Volumn 18, Issue 5, 2011, Pages

  Cai, Changmeng ^a   Balk, Steven P ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABIRATERONE; ANDROGEN RECEPTOR; ANDROSTANOLONE; CHOLESTEROL; DUTASTERIDE; FINASTERIDE; KETOCONAZOLE; TESTOSTERONE;

ADRENAL GLAND; ADRENAL SUPPRESSION; ADRENALECTOMY; ANDROGEN DEPRIVATION THERAPY; ANDROGEN METABOLISM; ANDROGEN SYNTHESIS; CASTRATION RESISTANT PROSTATE CANCER; HUMAN; MALE; PHASE 3 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; REVIEW; TESTOSTERONE SYNTHESIS; TREATMENT RESPONSE;

ANDROGENS; ANDROSTENOLS; ENZYME INHIBITORS; HUMANS; MALE; NEOPLASMS, HORMONE-DEPENDENT; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN;

EID: 80053940699     PISSN: 13510088     EISSN: 14796821     Source Type: Journal    
DOI: 10.1530/ERC-10-0339     Document Type: Review

References (50)

1. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ et al. 2010 Effect of dutasteride on the risk of prostate cancer. New England Journal of Medicine 362 1192-1202. (doi:10.1056/NEJMoa0908127)
2. Attard G, Reid AH, Olmos D & de Bono JS 2009 Antitumor activity with CYP17 blockade indicates that castration-resistant prostate cancer frequently remains hormone driven. Cancer Research 69 4937-4940. (doi:10.1158/0008-5472. CAN-08-4531)
3. Auchus RJ 2004 The backdoor pathway to dihydrotestosterone. Trends in Endocrinology and Metabolism 15 432-438. (doi:10.1016/S1043-2760(04)00214-0)
4. Bauman DR, Steckelbroeck S, Peehl DM & Penning TM 2006a Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer. Endocrinology 147 5806-5816. (doi:10.1210/en.2006-0627)
5. Bauman DR, Steckelbroeck S, Williams MV, Peehl DM & Penning TM 2006b Identification of the major oxidative 3alpha-hydroxysteroid dehydrogenase in human prostate that converts 5alpha-androstane-3alpha,17beta-diol to 5alpha-dihydrotestosterone: a potential therapeutic target for androgen-dependent disease. Molecular Endocrinology 20 444-458. (doi:10.1210/me.2005-0287)
6. Belanger B, Belanger A, Labrie F, Dupont A, Cusan L & Monfette G 1989 Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after castration: unique importance of extratesticular androgens in men. Journal of Steroid Biochemistry 32 695-698. (doi:10.1016/0022-4731(89)90514-1)
7. Belanger A, Pelletier G, Labrie F, Barbier O & Chouinard S 2003 Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends in Endocrinology and Metabolism 14 473-479. (doi:10.1016/j.tem.2003.10. 005)
8. Danila DC, Morris MJ, de Bono JS, Ryan CJ, Denmeade SR, Smith MR, Taplin ME, Bubley GJ, Kheoh T, Haqq C et al. 2010 Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. Journal of Clinical Oncology 28 1496-1501. (doi:10.1200/JCO.2009.25.9259)
9. Desmond JC, Mountford JC, Drayson MT, Walker EA, Hewison M, Ride JP, Luong QT, Hayden RE, Vanin EF & Bunce CM 2003 The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs. Cancer Research 63 505-512. (Pubitemid 36152514)
10. Dillard PR, Lin MF & Khan SA 2008 Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. Molecular and Cellular Endocrinology 295 115-120. (doi:10.1016/j.mce.2008.08.013)
11. El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F & Pelletier G 1999 Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry. Endocrinology 140 1481-1491. (doi:10.1210/en.140.3.1481)
12. Ettinger SL, Sobel R, Whitmore TG, Akbari M, Bradley DR, Gleave ME & Nelson CC 2004 Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Research 64 2212-2221. (doi:10.1158/0008-5472.CAN-2148-2)
13. Fleshner N, Gomella LG, Cookson MS, Finelli A, Evans A, Taneja SS, Lucia MS, Wolford E, Somerville MC & Rittmaster R 2007 Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial. Contemporary Clinical Trials 28 763-769. (doi:10.1016/j.cct.2007.05.006)
14. Fromont G, Chene L, Vidaud M, Vallancien G, Mangin P, Fournier G, Validire P, Latil A & Cussenot O 2005 Differential expression of 37 selected genes in hormonerefractory prostate cancer using quantitative taqman realtime RT-PCR. International Journal of Cancer 114 174-181. (doi:10.1002/ijc.20704)
15. Geller J 1985 Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. Seminars in Oncology 12 28-35. (Pubitemid 15149394)
16. Geller J & Albert J 1987 Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH). Urological Research 15 151-153. (doi:10.1007/BF00254427)
17. Geller J, Albert JD, Nachtsheim DA & Loza D 1984 Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. Journal of Urology 132 693-696. (Pubitemid 14017006)
18. Hamada A, Sissung T, Price DK, Danesi R, Chau CH, Sharifi N, Venzon D, Maeda K, Nagao K, Sparreboom A et al. 2008 Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-independent prostatic cancer. Clinical Cancer Research 14 3312-3318. (doi:10.1158/1078-0432.CCR-07-4118)
19. Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, Schroder FH & de Jong FH 2010 Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. Cancer Research 70 1256-1264. (doi:10.1158/0008-5472.CAN-09-2092)
20. Holzbeierlein J, Lal P, LaTulippe E, Smith A, Satagopan J, Zhang L, Ryan C, Smith S, Scher H, Scardino P et al. 2004 Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgenresponsive genes and mechanisms of therapy resistance. American Journal of Pathology 164 217-227. (doi:10.1016/S0002-9440(10)63112-4)
21. Ji Q, Chang L, VanDenBerg D, Stanczyk FZ & Stolz A 2003 Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. Prostate 54 275-289. (doi:10.1002/pros.10192)
22. Ji Q, Chang L, Stanczyk FZ, Ookhtens M, Sherrod A & Stolz A 2007 Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling. Cancer Research 67 1361-1369. (doi:10.1158/0008-5472.CAN-06-1593)
23. Labrie F, Luu-The V, Lin SX, Simard J & Labrie C 2000 Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends in Endocrinology and Metabolism 11 421-427. (doi:10. 1016/S1043-2760(00)00342-8)
24. Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA & Penning TM 1997 Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution. Molecular Endocrinology 11 1971-1984. (doi:10.1210/me.11.13.1971)
25. Lin HK, Steckelbroeck S, Fung KM, Jones AN & Penning TM 2004 Characterization of a monoclonal antibody for human aldo-keto reductase AKR1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase); immunohistochemical detection in breast and prostate. Steroids 69 795-801. (doi:10.1016/j.steroids.2004.09.014)
26. Lindstrom S, Adami HO, Balter KA, Xu J, Zheng SL, Stattin P, Gronberg H & Wiklund F 2007 Inherited variation in hormone-regulating genes and prostate cancer survival. Clinical Cancer Research 13 5156-5161. (doi:10.1158/1078-0432.CCR-07-0669)
27. Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, Ettinger SL, Gleave ME & Nelson CC 2008 Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Research 68 6407-6415. (doi:10.1158/0008-5472.CAN-07-5997)
28. Locke JA, Nelson CC, Adomat HH, Hendy SC, Gleave ME & Guns ES 2009 Steroidogenesis inhibitors alter but do not eliminate androgen synthesis mechanisms during progression to castration-resistance in LNCaP prostate xenografts. Journal of Steroid Biochemistry and Molecular Biology 115 126-136. (doi:10.1016/j.jsbmb.2009.03.011)
29. Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M & Sakai S 1998 Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. Journal of Biochemistry 124 940-946. (Pubitemid 28544904)
30. Mizokami A, Koh E, Fujita H, Maeda Y, Egawa M, Koshida K, Honma S, Keller ET & Namiki M 2004 The adrenal androgen androstenediol is present in prostate cancer tissue after androgen deprivation therapy and activates mutated androgen receptor. Cancer Research 64 765-771. (doi:10.1158/0008-5472.CAN-03- 0130)
31. Mohler JL, Gregory CW, Ford OH III, Kim D, Weaver CM, Petrusz P, Wilson EM & French FS 2004 The androgen axis in recurrent prostate cancer. Clinical Cancer Research 10 440-448. (doi:10.1158/1078-0432.CCR-1146-03)
32. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD & Nelson PS 2008 Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Research 68 4447-4454. (doi:10.1158/0008-5472.CAN-08-0249)
33. Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM et al. 2007 Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Research 67 5033-5041. (doi:10.1158/0008-5472.CAN-06-3332)
34. Mostaghel EA, Geng L, Holcomb I, Coleman IM, Lucas J, True LD & Nelson PS 2010 Variability in the androgen response of prostate epithelium to 5alpha-reductase inhibition: implications for prostate cancer chemoprevention. Cancer Research 70 1286-1295. (doi:10.1158/0008-5472.CAN-09-2509)
35. Nishiyama T, Hashimoto Y & Takahashi K 2004 The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer. Clinical Cancer Research 10 7121-7126. (doi:10.1158/1078-0432.CCR-04-0913)
36. Page ST, Lin DW, Mostaghel EA, Hess DL, True LD, Amory JK, Nelson PS, Matsumoto AM & Bremner WJ 2006 Persistent intraprostatic androgen concentrations after medical castration in healthy men. Journal of Clinical Endocrinology and Metabolism 91 3850-3856. (doi:10.1210/jc.2006-0968)
37. Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC, Molife LR, Hunt J, Messiou C, Parker C et al. 2010 Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. Journal of Clinical Oncology 28 1489-1495. (doi:10.1200/JCO.2009.24.6819)
38. Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR & Penning TM 2003 Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology 144 2922-2932. (doi:10.1210/en.2002-0032)
39. Sartor O, Nakabayashi M, Taplin ME, Ross RW, Kantoff PW, Balk SP & Oh WK 2009 Activity of dutasteride plus ketoconazole in castration-refractory prostate cancer after progression on ketoconazole alone. Clinical Genitourinary Cancer 7 E90-E92. (doi:10.3816/CGC.2009.n.030)
40. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG & Balk SP 2006 Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Research 66 2815-2825. (doi:10.1158/0008-5472.CAN-05-4000)
41. Steckelbroeck S, Jin Y, Gopishetty S, Oyesanmi B & Penning TM 2004 Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action. Journal of Biological Chemistry 279 10784-10795. (doi:10.1074/jbc.M313308200)
42. Taplin ME, Regan MM, Ko YJ, Bubley GJ, Duggan SE, Werner L, Beer TM, Ryan CW, Mathew P, Tu SM et al. 2009 Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clinical Cancer Research 15 7099-7105. (doi:10.1158/1078-0432.CCR-09-1722)
43. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM et al. 2003 The influence of finasteride on the development of prostate cancer. New England Journal of Medicine 349 215-224. (doi:10.1056/NEJMoa030660)
44. Titus MA, Gregory CW, Ford OH III, Schell MJ, Maygarden SJ & Mohler JL 2005a Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer. Clinical Cancer Research 11 4365-4371. (doi:10.1158/1078-0432.CCR-04- 0738)
45. Titus MA, Schell MJ, Lih FB, Tomer KB & Mohler JL 2005b Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clinical Cancer Research 11 4653-4657. (doi:10.1158/1078-0432.CCR-05-0525)
46. Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y & Nakagawa H 2008 Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Science 99 81-86. (Pubitemid 350239034)
47. Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, van Rooij HC, Trapman J, Brinkmann AO & Mulder E 1990 A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochemical and Biophysical Research Communications 173 534-540. (doi:10.1016/S0006-291X(05)80067-1)
48. van Weerden WM, Bierings HG, van Steenbrugge GJ, de Jong FH & Schroder FH 1992 Adrenal glands of mouse and rat do not synthesize androgens. Life Sciences 50 857-861. (doi:10.1016/0024-3205(92)90204-3)
49. Weihua Z, Lathe R, Warner M & Gustafsson JA 2002 An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane- 3beta,17beta-diol, and CYP7B1, regulates prostate growth. PNAS 99 13589-13594. (doi:10.1073/pnas.162477299)
50. Yuan X & Balk SP 2009 Mechanisms mediating androgen receptor reactivation after castration. Urologic Oncology 27 36-41. (doi:10.1016/j. urolonc.2008.03.021)