Molecular Oncology
Volume 1, Issue 4 , Pages 413-424 , April 2008

Androgens act synergistically to enhance estrogen-induced upregulation of human tissue kallikreins 10, 11, and 14 in breast cancer cells via a membrane bound androgen receptor

  • Miltiadis Paliouras

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    • Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, M5T 3L9 Canada
    • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, M5T 3L9 Canada
    • ,
  • Eleftherios P. Diamandis

      Affiliations

    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
    • Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, M5T 3L9 Canada
    • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray Street, Toronto, ON, M5T 3L9 Canada
    • Corresponding Author InformationCorresponding author. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 6th Floor, 60 Murray Street, Toronto, ON, M5T 3L9 Canada. Tel.: +1 416 586 8443; fax: +1 416 586 8628.

Received 30 October 2007 ,Revised 28 December 2007 ,Accepted 1 January 2008.

References 

  1. Aranda A, Pascual A. Nuclear hormone receptors and gene expression. Physiol. Rev. 2001;81:1269–1304
  2. Borgono CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat. Rev. Cancer. 2004;4:876–890
  3. Borgono CA, Grass L, Soosaipillai A, Yousef GM, Petraki CD, Howarth DH, et al. Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res. 2003;63:9032–9041
  4. Borgono CA, Michael IP, Diamandis EP. Human tissue kallikreins: physiologic roles and applications in cancer. Mol. Cancer Res. 2004;2:257–280
  5. Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J. Biol. Chem. 2001;276:9817–9824
  6. Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of osteoporotic fractures research group. Ann. Intern. Med. 1999;130:270–277
  7. Cinar B, Yeung F, Konaka H, Mayo MW, Freeman MR, Zhau HE, et al. Identification of a negative regulatory cis-element in the enhancer core region of the prostate-specific antigen promoter: implications for intersection of androgen receptor and nuclear factor-kappaB signalling in prostate cancer cells. Biochem. J. 2004;379:421–431
  8. Claessens F, Verrijdt G, Schoenmakers E, Haelens A, Peeters B, Verhoeven G, et al. Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation. J. Steroid Biochem. Mol. Biol. 2001;76:23–30
  9. Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J. Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J. Biol. Chem. 1996;271:6379–6388
  10. Cleutjens KB, van der Korput HA, van Eekelen CC, van Rooij HC, Faber PW, Trapman J. An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol. Endocrinol. 1997;11:148–161
  11. Cummings SR, Lee JS, Lui LY, Stone K, Ljung BM, Cauleys JA. Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study. Cancer Epidemiol. Biomarker Prev. 2005;14:1047–1051
  12. Erlanger BF, Borek F, Beiser SM, Lieberman S. Steroid-protein conjugates. I. Preparation and characterization of conjugates of bovine serum albumin with testosterone and with cortisone. J. Biol. Chem. 1957;228:713–727
  13. Erlanger BF, Borek F, Beiser SM, Lieberman S. Steroid-protein conjugates. II. Preparation and characterization of conjugates of bovine serum albumin with progesterone, deoxycorticosterone, and estrone. J. Biol. Chem. 1959;234:1090–1094
  14. Hackenberg R, Hofmann J, Holzel F, Schulz KD. Stimulatory effects of androgen and antiandrogen on the in vitro proliferation of human mammary carcinoma cells. J. Cancer Res. Clin. Oncol. 1988;114:593–601
  15. James VH, McNeill JM, Lai LC, Newton CJ, Ghilchik MW, Reed MJ. Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies. Steroids. 1987;50:269–279
  16. Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C, et al. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr. Relat. Cancer. 2005;12:1071–1082
  17. Kampa M, Nifli AP, Charalampopoulos I, Alexaki VI, Theodoropoulos PA, Stathopoulos EN, et al. Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp. Cell Res. 2005;307:41–51
  18. Kang HY, Cho CL, Huang KL, Wang JC, Hu YC, Lin HK, et al. Nongenomic androgen activation of phosphatidylinositol 3-kinase/Akt signaling pathway in MC3T3-E1 osteoblasts. J. Bone. Miner. Res. 2004;19:1181–1190
  19. Karaer O, Oruc S, Koyuncu FM. Aromatase inhibitors: possible future applications. Acta Obstet. Gynecol. Scand. 2004;83:699–706
  20. Klinge CM. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res. 2001;29:2905–2919
  21. Lacroix M, Leclercq G. Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Res. Treat. 2004;83:249–289
  22. Luo LY, Grass L, Diamandis EP. The normal epithelial cell-specific 1 (NES1) gene is up-regulated by steroid hormones in the breast carcinoma cell line BT-474. Anticancer Res. 2000;20:981–986
  23. Luo LY, Grass L, Diamandis EP. Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter. Clin. Chim. Acta. 2003;337:115–126
  24. Maggiolini M, Donze O, Jeannin E, Ando S, Picard D. Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha. Cancer Res. 1999;59:4864–4869
  25. Magklara A, Grass L, Diamandis EP. Differential steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in breast cancer cell lines. Breast Cancer Res. Treat. 2000;59:263–270
  26. Marshman E, Streuli CH. Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function. Breast Cancer Res. 2002;4:231–239
  27. McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv. Enzyme Regul. 2006;46:249–279
  28. Obiezu CV, Diamandis EP. Human tissue kallikrein gene family: applications in cancer. Cancer Lett. 2005;224:1–22
  29. Paliouras M, Diamandis EP. Coordinated steroid hormone-dependent and independent expression of multiple kallikreins in breast cancer cell lines. Breast Cancer Res. Treat. 2006;
  30. Paliouras M, Diamandis EP. The kallikrein world: an update on the human tissue kallikreins. Biol. Chem. 2006;387:643–652
  31. Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins: the cancer biomarker family. Cancer Lett. 2007;249:61–79
  32. Pampalakis G, Sotiropoulou G. Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer. Biol. Chem. 2006;387:773–782
  33. 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
  34. Perel E, Wilkins D, Killinger DW. The conversion of androstenedione to estrone, estradiol, and testosterone in breast tissue. J. Steroid Biochem. 1980;13:89–94
  35. Peterziel H, Mink S, Schonert A, Becker M, Klocker H, Cato AC. Rapid signalling by androgen receptor in prostate cancer cells. Oncogene. 1999;18:6322–6329
  36. Poulin R, Baker D, Labrie F. Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell line. Breast Cancer Res. Treat. 1988;12:213–225
  37. Recanatini M, Bisi A, Cavalli A, Belluti F, Gobbi S, Rampa A, et al. A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17, 20-lyase. J. Med. Chem. 2001;44:672–680
  38. Sidiropoulos M, Pampalakis G, Sotiropoulou G, Katsaros D, Diamandis EP. Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers. Tumor Biol. 2005;26:324–336
  39. Somboonporn W, Davis SR. Postmenopausal testosterone therapy and breast cancer risk. Maturitas. 2004;49:267–275
  40. Somboonporn W, Davis SR. Testosterone effects on the breast: implications for testosterone therapy for women. Endocr. Rev. 2004;25:374–388
  41. Stathopoulos EN, Dambaki C, Kampa M, Theodoropoulos PA, Anezinis P, Delakas D, et al. Membrane androgen binding sites are preferentially expressed in human prostate carcinoma cells. BMC. Clin. Pathol. 2003;3(1):
  42. Stein RA, McDonnell DP. Estrogen-related receptor alpha as a therapeutic target in cancer. Endocr. Relat. Cancer. 2006;13(Suppl. 1):S25–S32
  43. Stoica GE, Franke TF, Wellstein A, Czubayko F, List HJ, Reiter R, et al. Estradiol rapidly activates Akt via the ErbB2 signaling pathway. Mol. Endocrinol. 2003;17:818–830
  44. Stoica GE, Franke TF, Moroni M, Mueller S, Morgan E, Iann MC, et al. Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway. Oncogene. 2003;22:7998–8011
  45. Stover EP, Krishnan AV, Feldman D. Estrogen down-regulation of androgen receptors in cultured human mammary cancer cells (MCF-7). Endocrinology. 1987;120:2597–2603
  46. Sun M, Paciga JE, Feldman RI, Yuan Z, Coppola D, Lu YY, et al. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res. 2001;61:5985–5991
  47. Thijssen JH, Blankenstein MA, Donker GH, Daroszewski J. Endogenous steroid hormones and local aromatase activity in the breast. J. Steroid Biochem. Mol. Biol. 1991;39:799–804
  48. Tworoger SS, Missmer SA, Barbieri RL, Willett WC, Colditz GA, Hankinson SE. Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones. J. Natl. Cancer Inst. 2005;97:595–602
  49. Vilgelm A, Lian Z, Wang H, Beauparlant SL, Klein-Szanto A, Ellenson LH, et al. Akt-mediated phosphorylation and activation of estrogen receptor alpha is required for endometrial neoplastic transformation in Pten± mice. Cancer Res. 2006;66:3375–3380
  50. Walker G, MacLeod K, Williams AR, Cameron DA, Smyth JF, Langdon SP. Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin. Cancer Res. 2007;13:1438–1444
  51. Yousef GM, Diamandis EP. Human tissue kallikreins: a new enzymatic cascade pathway?. Biol. Chem. 2002;383:1045–1057
  52. Yousef GM, Borgono CA, Scorilas A, Ponzone R, Biglia N, Iskander L, et al. Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis. Br. J. Cancer. 2002;87:1287–1293
  53. Yousef GM, Scorilas A, Kyriakopoulou LG, Rendl L, Diamandis M, Ponzone R, et al. Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer. Clin. Chem. 2002;48:1241–1250
  54. Yu H, Diamandis EP, Levesque M, Giai M, Roagna R, Ponzone R, et al. Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue. Breast Cancer Res. Treat. 1996;40:171–178
  55. Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB. J. 2000;14:1725–1730
  56. Zhu YS, Cai LQ, Huang Y, Fish J, Wang L, Zhang ZK, et al. Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens. J. Androl. 2005;26:500–508discussion 509–510
  57. Zivadinovic D, Watson CS. Membrane estrogen receptor-alpha levels predict estrogen-induced ERK1/2 activation in MCF-7 cells. Breast Cancer Res. 2005;7:R130–R144

PII: S1574-7891(08)00002-1

doi: 10.1016/j.molonc.2008.01.001

Molecular Oncology
Volume 1, Issue 4 , Pages 413-424 , April 2008

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