Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation

Molecular and Cellular Endocrinology

Volumn 363, Issue 1-2, 2012, Pages 100-110

  Sirianni, Rosa ^a   Capparelli, Claudia ^a   Chimento, Adele ^a   Panza, Salvatore ^a   Catalano, Stefania ^a   Lanzino, Marilena ^a   Pezzi, Vincenzo ^a   Andò, Sebastiano ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

Author keywords

AAS; Anabolic androgens; Aromatase; Breast cancer; Estrogen receptors; IGF I

Indexed keywords

AROMATASE; CYCLIN D1; ESTRADIOL; ESTROGEN RECEPTOR; FULVESTRANT; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NANDROLONE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C; PROTEIN KINASE B; PROTEIN KINASE C; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; STANOZOLOL;

ARTICLE; BREAST CARCINOGENESIS; CANCER RISK; CCND1 GENE; CELL STRAIN MCF 7; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOPING; DRUG RECEPTOR BINDING; ENZYME ACTIVATION; ENZYME INDUCTION; ESTROGEN ACTIVITY; GENE; GENE EXPRESSION REGULATION; GENE INDUCTION; HORMONE SYNTHESIS; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UPREGULATION;

ANABOLIC AGENTS; ANDROGENS; AROMATASE; BREAST NEOPLASMS; CELL PROLIFERATION; CELL SURVIVAL; DRUG SYNERGISM; ENZYME INDUCTION; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; FEMALE; GENES, REPORTER; HUMANS; INSULIN-LIKE GROWTH FACTOR I; LUCIFERASES, RENILLA; MCF-7 CELLS; NANDROLONE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; STANOZOLOL; TYPE C PHOSPHOLIPASES; UP-REGULATION;

EID: 84866942650     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2012.08.002     Document Type: Article

References (63)

1. Arnold A., Papanikolaou A. Cyclin D1 in breast cancer pathogenesis. J. Clin. Oncol. 2005, 23:4215-4224.
2. Aspinall S.R., Stamp S., Davison A., Shenton B.K., Lennard T.W.J. The proliferative effects of 5-androstene-3[beta],17[beta]-diol and 5[alpha]-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines. J. Steroid Biochem. Mol. Biol. 2004, 88:37-51.
3. Basaria S., Wahlstrom J.T., Dobs A.S. Anabolic-androgenic steroid therapy in the treatment of chronic diseases. J. Clin. Endocrinol. Metab. 2001, 86:5108-5117.
4. Braunstein G.D. Management of female sexual dysfunction in postmenopausal women by testosterone administration: safety issues and controversies. J. Sex Med. 2007, 4:859-866.
5. Buckley M.F., Sweeney K.J., Hamilton J.A., Sini R.L., Manning D.L., Nicholson R.I., deFazio A., Watts C.K., Musgrove E.A., Sutherland R.L. Expression and amplification of cyclin genes in human breast cancer. Oncogene 1993, 8:2127-2133.
6. Bunone G., Briand P.A., Miksicek R.J., Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J. 1996, 15:2174-2183.
7. Calfee R., Fadale P. Popular ergogenic drugs and supplements in young athletes. Pediatrics 2006, 117:e577-589.
8. Catalano S., Barone I., Giordano C., Rizza P., Qi H., Gu G., Malivindi R., Bonofiglio D., Andò S. Rapid estradiol/ERα signaling enhances aromatase enzymatic activity in breast cancer cells. Mol. Endocrinol. 2009, 23:1634-1645.
9. Chimento A., Sirianni R., Zolea F., De Luca A., Lanzino M., Catalano S., Andò S., Pezzi V. Nandrolone and stanozolol induce Leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system. J. Cell Physiol. 2012, 227:2079-2088.
10. Chong Y.M., Williams S.L.J., Elkak A., Sharma A.K., Mokbel K. Insulin-like growth factor 1 (IGF-1) and its receptor mRNA Levels in breast cancer and adjacent non-neoplastic tissue. Anticancer Res. 2006, 26:167-173.
11. Chong Y., Colston K., Jiang W., Sharma A., Mokbel K. The relationship between the insulin-like growth factor-1 system and the oestrogen metabolising enzymes in breast cancer tissue and its adjacent non-cancerous tissue. Breast Cancer Res. Treat. 2006, 99:275-288.
12. Clark B.J., Wells J., King S.R., Stocco D.M. The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J. Biol. Chem. 1994, 269:28314-28322.
13. Cullen K.J., Yee D., Sly W.S., Perdue J., Hampton B., Lippman M.E., Rosen N. Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res. 1990, 50:48-53.
14. Dawson R. Drugs in sport - the role of the physician. J. Endocrinol. 2001, 170:55-61.
15. Ekena K., Katzenellenbogen J.A., Katzenellenbogen B.S. Determinants of ligand specificity of estrogen receptor-α: estrogen versus androgen discrimination. J. Biol. Chem. 1998, 273:693-699.
16. Evans N.A. Gym and tonic: a profile of 100 male steroid users. Br. J. Sports Med. 1997, 31:54-58.
17. Fitness, C.o.S.M.a., 1997. Adolescents and anabolic steroids: a subject review. Pediatrics 99, 904-908.
18. Foradori C.D., Weiser M.J., Handa R.J. Non-genomic actions of androgens. Front. Neuroendocrinol. 2008, 29:169-181.
19. Fournier M.A., Poirier D. Estrogen formation in endometrial and cervix cancer cell lines: involvement of aromatase, steroid sulfatase and 17 beta-hydroxysteroid dehydrogenases (types 1, 5, 7 and 12). Mol Cell Endocrinol. 2009, 301:142-145.
20. Gill K., Kirma N., Tekmal R.R. Overexpression of aromatase in transgenic male mice results in the induction of gynecomastia and other biochemical changes in mammary glands. J. Steroid Biochem. Mol. Biol. 2001, 77:13-18.
21. Hankinson S.E., Willett W.C., Colditz G.A., Hunter D.J., Michaud D.S., Deroo B., Rosner B., Speizer F.E., Pollak M. Circulating concentrations of insulin-like growth factor I and risk of breast cancer. Lancet 1998, 351:1393-1396.
22. Harada N. Aberrant expression of aromatase in breast cancer tissues. J. Steroid Biochem. Mol. Biol. 1997, 61:175-184.
23. Jerome L., Shiry L., Leyland-Jones B. Anti-insulin-like growth factor strategies in breast cancer. Semin. Oncol. 2004, 31:54-63.
24. Kanayama G., Hudson J.I., Pope H.G. Long-term psychiatric and medical consequences of anabolic-androgenic steroid abuse: a looming public health concern?. Drug Alcoh. Depend 2008, 98:1-12.
25. Katzenellenbogen B.S., Kendra K.L., Norman M.J., Berthois Y. Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res. 1987, 47:4355-4360.
26. Keen J.C., Davidson N.E. The biology of breast carcinoma. Cancer 2003, 97:825-833.
27. Kleinberg D., Barcellos-Hoff M. The pivotal role of insulin-like growth factor I in normal mammary development. Endocrinol. Metab. Clin. North Am. 2011, 40:461-471.
28. Labrie F., Luu-The V., Labrie C., Bélanger A., Simard J., Lin S.-X., Pelletier G. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocrine Rev. 2003, 24:152-182.
29. Lanzino M., Sisci D., Morelli C., Garofalo C., Catalano S., Casaburi I., Capparelli C., Giordano C., Giordano F., Maggiolini M., Andò S. Inhibition of cyclin D1 expression by androgen receptor in breast cancer cells: identification of a novel androgen response element. Nucleic Acids Res. 2010, 38:5351-5365.
30. Ma Q.L., Yang T.L., Yin J.Y., Peng Z.Y., Yu M., Liu Z.Q., Chen F.P. Role of insulin-like growth factor - 1 (IGF-1) in regulating cell cycle progression. Biochem. Biophys. Res. Commun. 2009, 389:150-155.
31. Maggiolini M., DonzŠ O., Jeannin E., Andò S., Picard D. Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α. Cancer Res. 1999, 59:4864-4869.
32. Miller W.R., Mullen P., Sourdaine P., Watson C., Dixon J.M., Telford J. Regulation of aromatase activity within the breast. J. Steroid Biochem. Mol. Biol. 1997, 61:193-202.
33. Missmer S.A., Eliassen A.H., Barbieri R.L., Hankinson S.E. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J. Natl. Cancer Inst. 2004, 96:1856-1865.
34. Ng S.T., Zhou J., Adesanya O.O., Wang J., LeRoith D., Bondy C.A. Growth hormone treatment induces mammary gland hyperplasia in aging primates. Nat. Med. 1997, 3:1141-1144.
35. Osborne C.K., Hobbs K., Clark G.M. Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice. Cancer Res. 1985, 45:584-590.
36. Pandini G., Genua M., Frasca F., Squatrito S., Vigneri R., Belfiore A. 17β-Estradiol up-regulates the insulin-like growth factor receptor through a nongenotropic pathway in prostate cancer cells. Cancer Res. 2007, 67:8932-8941.
37. Panno M.L., Mauro L., Marsico S., Bellizzi D., Rizza P., Morelli C., Salerno M., Giordano F., Ando' S. Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor α through its interaction with Sp1. J. Mol. Endocrinol. 2006, 36:91-105.
38. Peters A.A., Buchanan G., Ricciardelli C., Bianco-Miotto T., Centenera M.M., Harris J.M., Jindal S., Segara D., Jia L., Moore N.L., Henshall S.M., Birrell S.N., Coetzee G.A., Sutherland R.L., Butler L.M., Tilley W.D. Androgen receptor inhibits estrogen receptor-α activity and is prognostic in breast cancer. Cancer Res. 2009, 69:6131-6140.
39. Peyrat J., Bonneterre J., Hecquet B., Vennin P., Louchez M., Fournier C., Lefebvre J., Demaille A. Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur. J. Cancer 1993, 29A:492-497.
40. Prall O.W.J., Sarcevic B., Musgrove E.A., Watts C.K.W., Sutherland R.L. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J. Biol. Chem. 1997, 272:10882-10894.
41. Reznik Y., Dehennin L., Coffin C., Mahoudeau J., Leymarie P. Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation. J. Clin. Endocrinol. Metab. 2001, 86:146-150.
42. Rochefort H., Garcia M. Androgen on the estrogen receptor I - Binding and in vivo nuclear translocation. Steroids 1976, 28:549-560.
43. Rochefort H., Garcia M. The estrogenic and antiestrogenic activities of androgens in female target tissues. Pharmacol. Ther. 1983, 23:193-216.
44. Rubin R., Baserga R. Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis, and tumorigenicity. Lab. Invest. 1995, 73:311-331.
45. Santagati S., Gianazza E., Agrati P., Vegeto E., Patrone C., Pollio G., Maggi A. Oligonucleotide squelching reveals the mechanism of estrogen receptor autologous down-regulation. Mol. Endocrinol. 1997, 11:938-949.
46. Santen R.J., Brodie H., Simpson E.R., Siiteri P.K., Brodie A. History of aromatase: saga of an important biological mediator and therapeutic target. Endocrine Rev. 2009, 30:343-375.
47. Simpson E., Rubin G., Clyne C., Robertson K., O'Donnell L., Jones M., Davis S. The role of local estrogen biosynthesis in males and females. Trends Endocrinol. Metab. 2000, 11:184-188.
48. Sirianni R., Chimento A., Malivindi R., Mazzitelli I., Andò S., Pezzi V. Insulin-like growth factor-I, regulating aromatase expression through steroidogenic factor 1, supports estrogen-dependent tumor Leydig cell proliferation. Cancer Res. 2007, 67:8368-8377.
49. Sisci D., Morelli C., Garofalo C., Romeo F., Morabito L., Casaburi F., Middea E., Cascio S., Brunelli E., Andò S., Surmacz E. Expression of nuclear insulin receptor substrate 1 in breast cancer. J. Clin. Pathol. 2007, 60:633-641.
50. Socas L., Zumbado M., Perez-Luzardo O., Ramos A., PŠrez C., Hernandez J.R., Boada L.D. Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature. Br. J. Sports Med. 2005, 39:e27.
51. Somboonporn W., Davis S.R. Testosterone effects on the breast: implications for testosterone therapy for women. Endocrine Rev. 2004, 25:374-388.
52. Song R.X.D., Fan P., Yue W., Chen Y., Santen R.J. Role of receptor complexes in the extranuclear actions of estrogen receptor alpha in breast cancer. Endocr. Relat. Cancer 2006, 13:S3-13.
53. Sonne-Hansen K., Lykkesfeldt A.E. 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.
54. Sun X.Z., Zhou D., Chen S. Autocrine and paracrine actions of breast tumor aromatase. A three-dimensional cell culture study involving aromatase transfected MCF-7 and T-47D cells. J. Steroid Biochem. Mol. Biol. 1997, 63:29-36.
55. Sundaram K., Kumar N., Monder C., Bardin C.W. Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens. J. Steroid Biochem. Mol. Biol. 1995, 53:253-257.
56. Surmacz E. Function of the IGF-I receptor in breast cancer. J. Mammary Gland Biol. Neoplasia 2000, 5:95-105.
57. Tekmal R.R., Ramachandra N., Gubba S., Durgam V.R., Mantione J., Toda K., Shizuta Y., Dillehay D.L. Overexpression of int-5/aromatase in mammary glands of transgenic mice results in the induction of hyperplasia and nuclear abnormalities. Cancer Res. 1996, 56:3180-3185.
58. Tong G., Rajah T., Zang X., Pento J. The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells. Anticancer Res. 2002, 22:103-106.
59. Tora L., Mullick A., Metger D., Ponglikitmongkol M., Park I., Chambon P. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989, 8:1981-1986.
60. Trenton A.J., Currier G.W. Behavioural manifestations of anabolic steroid use. CNS Drugs 2005, 19:571-595.
61. Tworoger S.S., Missmer S.A., Barbieri R.L., Willett W.C., Colditz G.A., Hankinson S.E. Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones. J. Natl Cancer Inst. 2005, 97:595-602.
62. Yeh S., Hu Y.-C., Wang P.-H., Xie C., Xu Q., Tsai M.-Y., Dong Z., Wang R.-S., Lee T.-H., Chang C. Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J. Exp. Med. 2003, 198:1899-1908.
63. Yue W., Zhou D., Chen S., Brodie A. A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene. Cancer Res. 1994, 54:5092-5095.