Top

Published in:

01-02-2005 | Topic Paper

Mechanisms of the development of androgen independence in prostate cancer

Authors: Alan So, Martin Gleave, Antonio Hurtado-Col, Colleen Nelson

Published in: World Journal of Urology | Issue 1/2005

Abstract

The effectiveness of androgen ablation in the management of advanced prostate cancer is of limited duration, with the median length of response being only 18–24 months. The transition of the prostate cancer cell to an androgen independent phenotype is a complex process that involves selection and outgrowth of pre-existing clones of androgen-independent cells (clonal selection) as well as adaptive up-regulation of genes that help the cancer cells survive and grow after androgen ablation (adaptation). These two mechanisms share an important pre-requisite characteristic: prostate cancers are heterogeneous tumours comprised of various subpopulations of cells that respond differently to androgen withdrawal therapy. This tumour heterogeneity may reflect either a multifocal origin, adaptation to environmental stimuli, and/or genetic instability of the initial cancer. This review will reexamine the different mechanisms that enable prostate cancer cells to proliferate in an androgen depleted environment.

Isaacs JT (1999) The biology of hormone refractory prostate cancer. Why does it develop? Urol Clin North Am 26:263–273

Graff JR (2002) Emerging targets in the AKT pathway for treatment of androgen-independent prostatic adenocarcinoma. Expert Opin Ther Targets 6:103–113

Bostwick DG et al. (1998) Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma. Cancer 83:1995–2002CrossRef

Craft N et al. (1999) Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res 59:5030–5036

Ettinger SL et al. (2004) Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence. Cancer Res 64:2212–2221

Visakorpi T et al. (1995) In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 9:401–406CrossRef

Edwards J et al. (2003) Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 89:552–556CrossRef

Latil A et al. (2001) Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Cancer Res 61:1919–1926PubMed

Linja MJ et al. (2001) Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 61:3550–3555

10.

Ruizeveld de Winter J.A et al. (1994) Androgen receptor status in localized and locally progressive hormone refractory human prostate cancer. Am J Pathol 144:735–746

11.

Brown RS et al. (2002) Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer. J Pathol 198:237–244CrossRef

12.

Palmberg C et al. (2000) Androgen receptor gene amplification at primary progression predicts response to combined androgen blockade as second line therapy for advanced prostate cancer. J Urol 164:1992–1995CrossRef

13.

Chen CD et al. (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10:33–39CrossRef

14.

Gregory CW et al. (2001) Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res 61:2892–2898

15.

Gregory CW et al. (2001) A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res 61:4315–4319

16.

Koh E, Kanaya J, Namiki M (2001) Adrenal steroids in human prostatic cancer cell lines. Arch Androl 46:117–125CrossRef

17.

Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1:34–45CrossRef

18.

Newmark JR et al. (1992) Androgen receptor gene mutations in human prostate cancer. Proc Natl Acad Sci U S A 89:6319–6323

19.

Marcelli M et al. (2000) Androgen receptor mutations in prostate cancer. Cancer Res 60:944–949

20.

Taplin ME et al. (1999) Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res 59:2511–2515PubMed

21.

Taplin ME et al. (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 332:1393–1398CrossRef

22.

Koivisto PA et al. (1999) Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia. Clin Cancer Res 5:3578–3582

23.

Veldscholte J et al. (1992) The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. J Steroid Biochem Mol Biol 41:665–669CrossRef

24.

Suzuki H et al. (1996) Codon 877 mutation in the androgen receptor gene in advanced prostate cancer: relation to antiandrogen withdrawal syndrome. Prostate 29:153–158

25.

Fenton MA et al. (1997) Functional characterization of mutant androgen receptors from androgen-independent prostate cancer. Clin Cancer Res 3:1383–1388

26.

Culig Z et al. (1993) Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone. Mol Endocrinol 7:1541–1550CrossRef

27.

Zhao XY et al. (2000) Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med 6:703–706CrossRef

28.

Kelly WK (1998) Endocrine withdrawal syndrome and its relevance to the management of hormone refractory prostate cancer. Eur Urol 34 [Suppl 3]:18–23

29.

Yeh S, Chang C (1996) Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc Natl Acad Sci U S A 93:5517–5521CrossRef

30.

Miyamoto H et al. (1998) Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells. Proc Natl Acad Sci U S A 95:7379–7384CrossRef

31.

Gregory CW et al. (1998) Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res 58:5718–5724

32.

Fujimoto N et al. (1999) Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J Biol Chem 274:8316–8321CrossRef

33.

Bakin RE et al. (2003) Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells. Cancer Res 63:1981–1989

34.

Gnanapragasam VJ et al. (2001) Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer. Br J Cancer 85:1928–1936CrossRef

35.

Ueda T, Bruchovsky N, Sadar MD (2002) Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 277:7076–7085CrossRef

36.

Culig Z et al. (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54:5474–5478

37.

Culig Z et al. (1997) Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells. Prostate 32:106–114CrossRef

38.

Jongsma J et al. (2000) Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines. Prostate 42:34–44CrossRef

39.

Craft N et al. (1999) A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med 5:280–285CrossRef

40.

Hobisch A et al. (1998) Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 58:4640–4645

41.

Signoretti S et al. (2000) Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst 92:1918–1925CrossRef

42.

Shi Y et al. (2001) Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease. J Urol 166:1514–1519CrossRef

43.

Wen Y et al. (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res 60:6841–6845

44.

Zhou BP et al. (2000) HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem 275:8027–8031CrossRefPubMed

45.

Halvorsen OJ, Haukaas SA, Akslen LA (2003) Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer. Clin Cancer Res 9:1474–1479PubMed

46.

Zhou H et al. (2000) Akt regulates cell survival and apoptosis at a postmitochondrial level. J Cell Biol 151:483–494CrossRef

47.

Kulik G, Klippel A, Weber MJ (1997) Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol 17:1595–1606

48.

Li J, DeFea K, Roth RA (1999) Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem 274:9351–9356CrossRef

49.

Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34CrossRefPubMed

50.

Cohen P, Peehl DM, Rosenfeld RG (1994) The IGF axis in the prostate. Horm Metab Res 26:81–84

51.

Grimberg A, Cohen P (2000) Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183:1–9

52.

Thomas LN et al. (2000) Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and −5. Prostate 42:203–210

53.

Cohen P et al. (1994) Biological effects of prostate specific antigen as an insulin-like growth factor binding protein-3 protease. J Endocrinol 142:407–415

54.

Miyake H, Pollak M, Gleave ME (2000) Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models. Cancer Res 60:3058–3064

55.

Kiyama S et al. (2003) Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors. Cancer Res 63:3575–3584

56.

Miyake H et al. (2000) Overexpression of insulin-like growth factor binding protein-5 helps accelerate progression to androgen-independence in the human prostate LNCaP tumor model through activation of phosphatidylinositol 3’-kinase pathway. Endocrinology 141:2257–2265CrossRef

57.

McDonnell TJ et al. (1997) Expression of bcl-2 oncoprotein and p53 protein accumulation in bone marrow metastases of androgen independent prostate cancer. J Urol 157:569–574CrossRef

58.

Raffo AJ et al. (1995) Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 155:4438–4445

59.

Herbst RS, Frankel SR (2004) Oblimersen sodium (Genasense bcl-2 antisense oligonucleotide): a rational therapeutic to enhance apoptosis in therapy of lung cancer. Clin Cancer Res 10:4245s-4248s

60.

Hakansson A et al. (2003) Bcl-2 expression in metastatic malignant melanoma. Importance for the therapeutic efficacy of biochemotherapy. Cancer Immunol Immunother 52:249–254

61.

Chanan-Khan A, Czuczman MS (2004) Bcl-2 antisense therapy in B-cell malignant proliferative disorders. Curr Treat Options Oncol 5:261–267

62.

Leung S et al. (2001) Synergistic chemosensitization and inhibition of progression to androgen independence by antisense Bcl-2 oligodeoxynucleotide and paclitaxel in the LNCaP prostate tumor model. Int J Cancer 91:846–850CrossRef

63.

Miayake H, Tolcher A, Gleave ME ( 2000) Chemosensitization and delayed androgen-independent recurrence of prostate cancer with the use of antisense Bcl-2 oligodeoxynucleotides. J Natl Cancer Inst 92:34–41CrossRef

64.

Miyake H, Monia BP, Gleave ME (2000) Inhibition of progression to androgen-independence by combined adjuvant treatment with antisense BCL-XL and antisense Bcl-2 oligonucleotides plus taxol after castration in the Shionogi tumor model. Int J Cancer 86(:855–862

65.

Steinberg J et al. (1997) Intracellular levels of SGP-2 (clusterin) correlate with tumor grade in prostate cancer. Clin Cancer Res 3:1707–1711

66.

Cervellera M et al. (2000) Direct transactivation of the anti-apoptotic gene apolipoprotein J (clusterin) by B-MYB. J Biol Chem 275:21055–21060CrossRef

67.

Kyprianou N et al. (1991) Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 51:162–166

68.

Redondo M et al. (2000) Overexpression of clusterin in human breast carcinoma. Am J Pathol 157:393–399

69.

Wellmann A et al. (2000) Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas. Blood 96:398–404

70.

Parczyk K et al. (1994) Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas. J Cancer Res Clin Oncol 120:186–188

71.

Calero M et al. (2000) Apolipoprotein J (clusterin) and Alzheimer’s disease. Microsc Res Tech 50:305–315

72.

Rosenberg ME, Silkensen J (1995) Clusterin: physiologic and pathophysiologic considerations. Int J Biochem Cell Biol 27:633–645CrossRef

73.

Montpetit ML, Lawless KR, Tenniswood M (1986) Androgen-repressed messages in the rat ventral prostate. Prostate 8:25–36

74.

Miyake H et al. (2000) Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer Res 60:170–176

75.

Bubendorf L et al. (1999) Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays. J Natl Cancer Inst 91:1758–1764CrossRef

76.

July LV et al. (2002) Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. Prostate 50:179–188CrossRef

77.

Tenniswood MP et al. (1992) Active cell death in hormone-dependent tissues. Cancer Metastasis Rev 11:197–220CrossRef

78.

Danik M et al. (1991) Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death. Proc Natl Acad Sci U S A 88:8577–8581

79.

Connor J et al. (1991) SGP-2 expression as a genetic marker of progressive cellular pathology in experimental hydronephrosis. Kidney Int 39:1098–1103

80.

Ho SM et al. (1998) Lack of association between enhanced TRPM-2/clusterin expression and increased apoptotic activity in sex-hormone-induced prostatic dysplasia of the Noble rat. Am J Pathol 153:131–139

81.

Schwochau GB, Nath KA, Rosenberg ME (1998) Clusterin protects against oxidative stress in vitro through aggregative and nonaggregative properties. Kidney Int 53:1647–1653CrossRefPubMed

82.

French LE et al. (1992) Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus. J Clin Invest 90:1919–1925

83.

Wilson MR Easterbrook-Smith SB (2000) Clusterin is a secreted mammalian chaperone. Trends Biochem Sci 25:95–98CrossRefPubMed

84.

Humphreys DT et al. (1999) Clusterin has chaperone-like activity similar to that of small heat shock proteins. J Biol Chem 274:6875–6881CrossRef

85.

Sensibar JA et al. (1995) Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res 55:2431–2437

86.

Miyake H et al. (2000) Acquisition of chemoresistant phenotype by overexpression of the antiapoptotic gene testosterone-repressed prostate message-2 in prostate cancer xenograft models. Cancer Res 60:2547–2554

87.

Miyake H et al. (2003) Resistance to cytotoxic chemotherapy-induced apoptosis in human prostate cancer cells is associated with intracellular clusterin expression. Oncol Rep 10:469–473

88.

Rocchi P, So A, Kojima S, Signaevsky M, Beraldi E, Fazli L, Hurtado-Coll A, Yamanaka K, Gleave M (2004) Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer. Cancer Res 64:6595–65602

Title: Mechanisms of the development of androgen independence in prostate cancer
Authors: Alan So
Martin Gleave
Antonio Hurtado-Col
Colleen Nelson
Publication date: 01-02-2005
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 1/2005
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-004-0473-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mechanisms of the development of androgen independence in prostate cancer

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2005

Rationale for the development and current status of calcitriol in androgen-independent prostate cancer

Sacral colpopexy using mersilene mesh in the treatment of vaginal vault prolapse

The role of bisphosphonates in hormone-refractory prostate cancer

Targeting Bcl-2 with oblimersen for patients with hormone refractory prostate cancer

Clinical characterization of the prostatitis patient in Italy: a prospective urology outpatient study

Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer