The role of androgens in normal and malignant breast tissue

Breast Care

Volumn 3, Issue 5, 2008, Pages 325-331

  Tiefenbacher, Katharina ^a   Daxenbichler, Günter ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Androgens; Breast; Breast cancer; Paracrine mechanisms

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; ANDROSTANOLONE; ANTIESTROGEN; AROMATASE INHIBITOR; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TESTOSTERONE; TESTOSTERONE PROPIONATE;

ANDROGEN BLOOD LEVEL; ANDROGEN INSENSITIVITY SYNDROME; BREAST CANCER; BREAST DEVELOPMENT; DRUG EFFECT; HORMONE ACTION; HORMONE RESPONSE; HUMAN; PRIORITY JOURNAL; REVIEW; TESTOSTERONE BLOOD LEVEL;

EID: 56249145138     PISSN: 16613791     EISSN: 16613805     Source Type: Journal    
DOI: 10.1159/000158055     Document Type: Review

References (82)

1. Dunn JF, Nisula BC, Rodbard D: Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 1981;53:58-68.
2. Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE: Role of endocytosis in cellular uptake of sex steroids. Cell 2005;122:751-762.
3. Rowling MJ, Kemmis CM, Taffany DA, Welsh J: Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. J Nutr 2006;136:2754-2759.
4. Labrie F: Intracrinology. Mol Cell Endocrinol 1991;78:C113-C118.
5. Tobacman JK, Hinkhouse M, Khalkhali-Ellis Z: Steroid sulfatase activity and expression in mammary myoepithelial cells. J Steroid Biochem Mol Biol 2002;81:65-68.
6. Suzuki T, Miki Y, Nakata T, Shiotsu Y, Akinaga S, Inoue K, Ishida T, Kimura M, Moriya T, Sasano H: Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. J Steroid Biochem Mol Biol 2003;86:449-454.
7. Miki Y, Nakata T, Suzuki T, Darnel AD, Moriya T, Kaneko C, Hidaka K, Shiotsu Y, Kusaka H, Sasano H: Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues. J Clin Endocrinol Metab 2002;87:5760-5768.
8. Evans TR, Rowlands MG, Law M, Coombes RC: Intratumoral oestrone sulphatase activity as a prognostic marker in human breast carcinoma. Br J Cancer 1994;69:555-561.
9. Zaichuk T, Ivancic D, Scholtens D, Schiller C, Khan SA: Tissue-specific transcripts of human steroid sulfatase are under control of estrogen signaling pathways in breast carcinoma. J Steroid Biochem Mol Biol 2007;105:76-84.
10. Reed MJ, Purohit A, Woo LWL, Newman SP, Potter BVL: Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr Rev 2005;26:171-202.
11. Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR: Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol 2000;72:23-27.
12. Luu The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F: Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase. Mol Endocrinol 1989;3:1310-1312.
13. Gingras S, Moriggl R, Groner B, Simard J: Induction of 3beta-hydroxysteroid dehydrogenase/delta 5-delta4 isomerase type 1 gene transcription in human breast cancer cell lines and in normal mammary epithelial cells by interleukin-4 and interleukin-13. Mol Endocrinol 1999;13:66-81.
14. Pelletier G, Luu-The V, El-Alfy M, Li S, Labrie F: Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland. J Mol Endocrinol 2001;26:11-19.
15. Day JM, Tutill HJ, Purohit A, Reed MJ: Design and validation of specific inhibitors of 17{beta}-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis. Endocr Relat Cancer 2008;15:665-692.
16. Labrie F, Luu-The V, Labrie C, Bélanger A, Simard J, Lin S, Pelletier G: Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 2003;24:152-182.
17. Purohit A, Tutill HJ, Day JM, Chander SK, Lawrence HR, Allan GM, Fischer DS, Vicker N, Newman SP, Potter BVL, Reed MJ: The regulation and inhibition of 17beta-hydroxysteroid dehydrogenase in breast cancer. Mol Cell Endocrinol 2006;248:199-203.
18. Miettinen M, Mustonen M, Poutanen M, Isomaa V, Wickman M, Söderqvist G, Vihko R, Vihko P: 17Beta-hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue. Breast Cancer Res Treat 1999;57:175-182.
19. Nguyen BL, Chetrite G, Pasqualini JR: Transformation of estrone and estradiol in hormone-dependent and hormone-independent human breast cancer cells. Effects of the antiestrogen ICI 164,384, danazol, and promegestone (R-5020). Breast Cancer Res Treat 1995;34:139-146.
20. Day JM, Foster PA, Tutill HJ, Parsons MFC, Newman SP, Chander SK, Allan GM, Lawrence HR, Vicker N, Potter BVL, Reed MJ, Purohit A: 17Beta-hydroxysteroid dehydrogenase type 1, and not type 12, is a target for endocrine therapy of hormone-dependent breast cancer. Int J Cancer 2008;122:1931-1940.
21. Song D, Liu G, Luu-The V, Zhao D, Wang L, Zhang H, Xueling G, Li S, Désy L, Labrie F, Pelletier G: Expression of aromatase and 17beta-hydroxysteroid dehydrogenase types 1, 7 and 12 in breast cancer. An immunocytochemical study. J Steroid Biochem Mol Biol 2006;101:136-144.
22. Gangloff A, Shi R, Nahoum V, Lin S: Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase. FASEB J 2003;17:274-276.
23. Suzuki T, Miki Y, Moriya T, Akahira J, Ishida T, Hirakawa H, Yamaguchi Y, Hayashi S, Sasano H: 5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer 2007;120:285-291.
24. Suzuki T, Moriya T, Ariga N, Kaneko C, Kanazawa M, Sasano H: 17Beta-hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: a correlation to clinicopathological parameters. Br J Cancer 2000;82:518-523.
25. Gunnarsson C, Hellqvist E, Stål O: 17Beta-hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer. Br J Cancer 2005;92:547-552.
26. Wiebe JP, Muzia D, Hu J, Szwajcer D, Hill SA, Seachrist JL: The 4-pregnene and 5alpha-pregnane progesterone metabolites formed in nontumorous and tumorous breast tissue have opposite effects on breast cell proliferation and adhesion. Cancer Res 2000;60:936-943.
27. Brodie A, Lu Q, Nakamura J: Aromatase in the normal breast and breast cancer. J Steroid Biochem Mol Biol 1997;61:281-286.
28. Santen RJ, Martel J, Hoagland M, Naftolin F, Roa L, Harada N, Hafer L, Zaino R, Santner SJ: Stromal spindle cells contain aromatase in human breast tumors. J Clin Endocrinol Metab 1994;79:627-632.
29. Miki Y, Suzuki T, Sasano H: Controversies of aromatase localization in human breast cancer - stromal versus parenchymal cells. J Steroid Biochem Mol Biol 2007;106:97-101.
30. Sonne-Hansen K, Lykkesfeldt AE: Endogenous aromatization of testosterone results in growth stimulation of the human MCF-7 breast cancer cell line. J Steroid Biochem Mol Biol 2005;93:25-34.
31. Zhuang Y, Saaristo R, Ylikomi T: An in vitro long-term culture model for normal human mammary gland: expression and regulation of steroid receptors. Cell Tissue Res 2003;311:217-226.
32. Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH: Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 1991;39:927-936.
33. Kimura N, Mizokami A, Oonuma T, Sasano H, Nagura H: Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 1993;41:671-678.
34. Janssen PJ, Brinkmann AO, Boersma WJ, Van der Kwast TH: Immunohistochemical detection of the androgen receptor with monoclonal antibody F39.4 in routinely processed, paraffin-embedded human tissues after microwave pre-treatment. J Histochem Cytochem 1994;42:1169-1175.
35. Birrell SN, Butler LM, Harris JM, Buchanan G, Tilley WD: Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer. FASEB J 2007;21:2285-2293.
36. Riva C, Dainese E, Caprara G, Rocca PC, Massarelli G, Tot T, Capella C, Eusebi V: Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma. Virchows Arch 2005;447:695-700.
37. Narita D, Raica M, Suciu C, Cîmpean A, Anghel A: Immunohistochemical expression of androgen receptor and prostate-specific antigen in breast cancer. Folia Histochem Cytobiol 2006;44:165-172.
38. Kuenen-Boumeester V, Van der Kwast TH, van Putten WL, Claassen C, van Ooijen B, Henzen-Logmans SC: Immunohistochemical determination of androgen receptors in relation to oestrogen and progesterone receptors in female breast cancer. Int J Cancer 1992;52:581-584.
39. Isola JJ: Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol 1993;170:31-35.
40. Gonzalez LO, Corte MD, Vazquez J, Junquera S, Sanchez R, Alvarez AC, Rodriguez JC, Lamelas ML, Vizoso FJ: Androgen receptor expression in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 2008;8:149.
41. Suzuki T, Miki Y, Moriya T, Akahira J, Hirakawa H, Ohuchi N, Sasano H: In situ production of sex steroids in human breast carcinoma. Med Mol Morphol 2007;40:121-127.
42. Shibuya R, Suzuki T, Miki Y, Yoshida K, Moriya T, Ono K, Akahira J, Ishida T, Hirakawa H, Evans DB, Sasano H: Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast. Endocr Relat Cancer 2008;15:113-124.
43. Secreto G, Venturelli E, Bucci A, Piromalli D, Fariselli G, Galante E: Intratumour amount of sex steroids in elderly breast cancer patients. An approach to the biological characterization of mammary tumours in the elderly. J Steroid Biochem Mol Biol 1996;58:557-561.
44. Recchione C, Venturelli E, Manzari A, Cavalleri A, Martinetti A, Secreto G: Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues. J Steroid Biochem Mol Biol 1995;52:541-546.
45. Mistry P, Griffiths K, Maynard PV: Endogenous C19-steroids and oestradiol levels in human primary breast tumour tissues and their correlation with androgen and oestrogen receptors. J Steroid Biochem 1986;24:1117-1125.
46. van Landeghem AA, Poortman J, Nabuurs M, Thijssen JH: Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 1985;45:2900-2906.
47. Blankenstein MA, van de Ven J, Maitimu-Smeele I, Donker GH, de Jong PC, Daroszewski J, Szymczak J, Milewicz A, Thijssen JH: Intratumoral levels of estrogens in breast cancer. J Steroid Biochem Mol Biol 1999;69:293-297.
48. 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.
49. Dimitrakakis C, Zhou J, Wang J, Belanger A, LaBrie F, Cheng C, Powell D, Bondy C: A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause 2003;10:292-298.
50. Jayo MJ, Register TC, Hughes CL, Blas-Machado U, Sulistiawati E, Borgerink H, Johnson CS: Effects of an oral contraceptive combination with or without androgen on mammary tissues: a study in rats. J Soc Gynecol Investig 2000;7:257-265.
51. Hofling M, Hirschberg AL, Skoog L, Tani E, Hägerström T, von Schoultz B: Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women. Menopause 2007;14:183-190.
52. Moore E, Wisniewski A, Dobs A: Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects. J Clin Endocrinol Metab 2003;88:3467-3473.
53. Mueller A, Kiesewetter F, Binder H, Beckmann MW, Dittrich R: Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals. J Clin Endocrinol Metab 2007;92: 3470-3475.
54. Sapino A, Pietribiasi F, Godano A, Bussolati G: Effect of long-term administration of androgens on breast tissues of female-to-male transsexuals. Ann N Y Acad Sci 1990;586:143-145.
55. Futterweit W, Schwartz IS: Histopathology of the breasts of 12 women receiving long-term exogenous androgen therapy. Mt Sinai J Med 1988;55:309-312.
56. Slagter MH, Gooren LJG, Scorilas A, Petraki CD, Diamandis EP: Effects of long-term androgen administration on breast tissue of female-to-male transsexuals. J Histochem Cytochem 2006;54:905-910.
57. Burgess HE, Shousha S: An immunohistochemical study of the long-term effects of androgen administration on female-to-male transsexual breast: a comparison with normal female breast and male breast showing gynaecomastia. J Pathol 1993;170:37-43.
58. Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS: Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev 1995;16:271-321.
59. New MI: An update of congenital adrenal hyperplasia. Ann N Y Acad Sci 2004;1038:14-43.
60. Somboonporn W, Davis SR: Testosterone effects on the breast: implications for testosterone therapy for women. Endocr Rev 2004;25:374-388.
61. Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T: Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol Endocrinol 2002;16:113-120.
62. Birrell SN, Bentel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD: Androgens induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol 1995;52:459-467.
63. Lapointe J, Fournier A, Richard V, Labrie C: Androgens down-regulate bcl-2 protooncogene expression in ZR-75-1 human breast cancer cells. Endocrinology 1999;140:416-421.
64. Hatzoglou A, Kampa M, Kogia C, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, Gravanis A, Castanas E: Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab 2005;90:893-903.
65. Chamberlain NL, Driver ED, Miesfeld RL: The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994;22:3181-3186.
66. González A, Javier Dorta F, Rodriguez G, Brito B, Rodríguez MADC, Cabrera A, Díaz-Chico JC, Reyes R, Aguirre-Jaime A, Nicolás Díaz-Chico B: Increased risk of breast cancer in women bearing a combination of large CAG and GGN repeats in the exon 1 of the androgen receptor gene. Eur J Cancer 2007;43:2373-2380.
67. Wang W, John EM, Ingles SA: Androgen receptor and prostate-specific antigen gene polymorphisms and breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev 2005;14:2990-2994.
68. Cox DG, Blanché H, Pearce CL, Calle EE, Colditz GA, Pike MC, Albanes D, Allen NE, Amiano P, Berglund G, Boeing H, Buring J, Burtt N, Canzian F, Chanock S, Clavel-Chapelon F, Feigelson HS, Freedman M, Haiman CA, Hankinson SE, Henderson BE, Hoover R, Hunter DJ, Kaaks R, Kolonel L, Kraft P, LeMarchand L, Lund E, Palli D, Peeters PHM, Riboli E, Stram DO, Thun M, Tjonneland A, Trichopoulos D, Yeager M: A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Breast Cancer Res 2006;8:R54.
69. Wooster R, Mangion J, Eeles R, Smith S, Dowsett M, Averill D, Barrett-Lee P, Easton DF, Ponder BA, Stratton MR: A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nat Genet 1992;2:132-134.
70. López-Capapé M, Alonso M, Gonçalves J, Barrio R: [Partial androgen insensitivity syndrome associated with familiar breast cancer]. Med Clin (Barc) 2005;124:598-599.
71. Lobaccaro JM, Lumbroso S, Belon C, Galtier-Dereure F, Bringer J, Lesimple T, Namer M, Cutuli BF, Pujol H, Sultan C: Androgen receptor gene mutation in male breast cancer. Hum Mol Genet 1993;2:1799-1802.
72. Poujol N, Lobaccaro JM, Chiche L, Lumbroso S, Sultan C: Functional and structural analysis of R607Q and R608K androgen receptor substitutions associated with male breast cancer. Mol Cell Endocrinol 1997;130:43-51.
73. Hiort O, Naber SP, Lehners A, Muletta-Feurer S, Sinnecker GH, Zöllner A, Komminoth P: The role of androgen receptor gene mutations in male breast carcinoma. J Clin Endocrinol Metab 1996;81:3404-3407.
74. Gottlieb B, Beitel LK, Wu JH, Trifiro M: The androgen receptor gene mutations database (ARDB): 2004 update. Hum Mutat 2004;23:527-533.
75. Zhu X, Daffada AA, Chan CM, Dowsett M: Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer. Int J Cancer 1997;72:574-580.
76. Shan L, Yang Q, Nakamura M, Nakamura Y, Mori I, Sakurai T, Kakudo K: Active allele loss of the androgen receptor gene contributes to loss of androgen receptor expression in female breast cancers. Biochem Biophys Res Commun 2000;275:488-492.
77. Secreto G, Toniolo P, Pisani P, Recchione C, Cavalleri A, Fariselli G, Totis A, Di Pietro S, Berrino F: Androgens and breast cancer in premenopausal women. Cancer Res 1989;49:471-476.
78. Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PHM, Biessy C, Dossus L, Lukanova A, Bingham S, Khaw K, Allen NE, Bueno-de-Mesquita HB, van Gils CH, Grobbee D, Boeing H, Lahmann PH, Nagel G, Chang-Claude J, Clavel-Chapelon F, Fournier A, Thiébaut A, González CA, Quirós JR, Tormo M, Ardanaz E, Amiano P, Krogh V, Palli D, Panico S, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Ferrari P, Norat T, Saracci R, Riboli E: Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 2005;12:1071-1082.
79. Rudlowski C: Male breast cancer. Breast Care 2008;3:183-189.
80. Goldenberg IS, Sedransk N, Volk H, Segaloff A, Kelley RM, Haines CR: Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group. Cancer 1975;36:308-310.
81. Karydas I, Fentiman IS, Tong D, Bulbrook RD, Hayward JL: Adjuvant androgen treatment of operable breast cancer - a 20 year analysis. Eur J Surg Oncol 1987;13:113-117.
82. Garreau JR, Muller P, Pommier R, Pommier S: Transgenic introduction of androgen receptor into estrogen-receptor-, progesterone-receptor-, and androgen-receptor-negative breast cancer cells renders them responsive to hormonal manipulation. Am J Surg 2006;191:576-580.