The growth response to androgen receptor signaling in ERα-negative human breast cells is dependent on p21 and mediated by MAPK activation

Breast Cancer Research

Volumn 14, Issue 1, 2012, Pages

  Garay, Joseph P ^a   Karakas, Bedri ^a   Abukhdeir, Abde M ^a   Cosgrove, David P ^a   Gustin, John P ^a,b   Higgins, Michaela J ^a   Konishi, Hiroyuki ^a   Konishi, Yuko ^a   Lauring, Josh ^a   Mohseni, Morassa ^a   Wang, Grace M ^a   Jelovac, Danijela ^a   Weeraratna, Ashani ^c   Sherman Baust, Cheryl A ^c   Morin, Patrice J ^c   Toubaji, Antoun ^a   Meeker, Alan ^a   De Marzo, Angelo M ^a   Lewis, Gloria ^a   Subhawong, Andrea ^a   Argani, Pedram ^a   Park, Ben H ^a,b   more..

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b Johns Hopkins University   (United States)

^c NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; COMPLEMENTARY DNA; EPIDERMAL GROWTH FACTOR; ESTROGEN RECEPTOR ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN P21; ANDROGEN; ANILIDE; ANTIANDROGEN; BICALUTAMIDE; CCND1 PROTEIN, HUMAN; CDKN1A PROTEIN, HUMAN; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 1A; ESTROGEN RECEPTOR ALPHA, HUMAN; METRIBOLONE; NITRILE; RECOMBINANT PROTEIN; TOLUENESULFONIC ACID DERIVATIVE;

ANDROGEN RECEPTOR SIGNALING; ARTICLE; BREAST CANCER; CANCER GROWTH; CELL PROLIFERATION; CELL STRAIN MCF 10A; CELL STRAIN MDA MB 231; CONTROLLED STUDY; ENZYME ACTIVATION; EPITHELIUM CELL; GENE INACTIVATION; HUMAN; HUMAN CELL; LIGAND BINDING; MOLECULAR CLONING; PROTEIN INDUCTION; RECEPTOR BINDING; SIGNAL TRANSDUCTION; TRANSGENE; TUMOR CELL LINE; BIOSYNTHESIS; BREAST TUMOR; DRUG EFFECT; FEMALE; GENE EXPRESSION; GENETICS; METABOLISM; PHYSIOLOGY; UPREGULATION;

ANDROGEN ANTAGONISTS; ANDROGENS; ANILIDES; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN D1; CYCLIN-DEPENDENT KINASE INHIBITOR P21; ENZYME ACTIVATION; EPITHELIAL CELLS; ESTROGEN RECEPTOR ALPHA; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FEMALE; GENE EXPRESSION; HUMANS; MAP KINASE SIGNALING SYSTEM; METRIBOLONE; NITRILES; RECEPTORS, ANDROGEN; RECOMBINANT PROTEINS; TOSYL COMPOUNDS; UP-REGULATION;

EID: 84862806100     PISSN: 14655411     EISSN: 1465542X     Source Type: Journal    
DOI: 10.1186/bcr3112     Document Type: Article

References (64)

1. van de Velde CJ, Verma S, van Nes JG, Masterman C, Pritchard KI. Switching from tamoxifen to aromatase inhibitors for adjuvant endocrine therapy in postmenopausal patients with early breast cancer. Cancer Treat Rev 2009,
2. 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.
3. Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL, Speizer FE. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1998, 90:1292-1299. 10.1093/jnci/90.17.1292, 9731736.
4. Dimitrakakis C, Bondy C. Androgens and the breast. Breast Cancer Res 2009, 11:212. 10.1186/bcr2413, 2790857, 19889198.
5. Lea OA, Kvinnsland S, Thorsen T. Improved measurement of androgen receptors in human breast cancer. Cancer Res 1989, 49:7162-7167.
6. Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer 2003, 98:703-711. 10.1002/cncr.11532, 12910513.
7. Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ. Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 2003, 120:725-731. 10.1309/42F00D0DJD0J5EDT, 14608899.
8. Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS. Expression of androgen receptors in primary breast cancer. Ann Oncol 2010, 21:488-492. 10.1093/annonc/mdp510, 19887463.
9. Niemeier LA, Dabbs DJ, Beriwal S, Striebel JM, Bhargava R. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol 2010, 23:205-212. 10.1038/modpathol.2009.159, 19898421.
10. Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 2011, 17:1867-1874. 10.1158/1078-0432.CCR-10-2021, 21325075.
11. Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, Jindal S, Segara D, Jia L, Moore NL, Henshall SM, Birrell SN, Coetzee GA, Sutherland RL, Butler LM, Tilley WD. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res 2009, 69:6131-6140.
12. Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS, Viale G, Sapino A. Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat 2010, 124:607-617. 10.1007/s10549-010-0761-y, 20127405.
13. Buchanan G, Birrell SN, Peters AA, Bianco-Miotto T, Ramsay K, Cops EJ, Yang M, Harris JM, Simila HA, Moore NL, Bentel JM, Ricciardelli C, Horsfall DJ, Butler LM, Tilley WD. Decreased androgen receptor levels and receptor function in breast cancer contribute to the failure of response to medroxyprogesterone acetate. Cancer Res 2005, 65:8487-8496. 10.1158/0008-5472.CAN-04-3077, 16166329.
14. Lonning PE. Additive endocrine therapy for advanced breast cancer - back to the future. Acta Oncol 2009, 48:1092-1101. 10.3109/02841860903117816, 19863216.
15. Gucalp A, Traina TA. Triple-negative breast cancer: role of the androgen receptor. Cancer J 2010, 16:62-65. 10.1097/PPO.0b013e3181ce4ae1, 20164692.
16. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011, 121:2750-2767. 10.1172/JCI45014, 3127435, 21633166.
17. Robinson JL, Macarthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, Carroll JS. Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. Embo J 2011, 30:3019-3027. 10.1038/emboj.2011.216, 21701558.
18. Naderi A, Chia KM, Liu J. Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer. Breast Cancer Res 2011, 13:R36. 10.1186/bcr2858, 3219199, 21457548.
19. Nahleh Z. Androgen receptor as a target for the treatment of hormone receptor-negative breast cancer: an unchartered territory. Future Oncol 2008, 4:15-21. 10.2217/14796694.4.1.15, 18240997.
20. Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell 2011, 20:119-131. 10.1016/j.ccr.2011.05.026, 21741601.
21. Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med 1958, 259:673-675. 10.1056/NEJM195810022591404, 13590423.
22. 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. 10.1016/0960-0760(95)00005-K, 7748811.
23. Yoon DS, Wersto RP, Zhou W, Chrest FJ, Garrett ES, Kwon TK, Gabrielson E. Variable levels of chromosomal instability and mitotic spindle checkpoint defects in breast cancer. Am J Pathol 2002, 161:391-397. 10.1016/S0002-9440(10)64194-6, 1850727, 12163363.
24. De Amicis F, Thirugnansampanthan J, Cui Y, Selever J, Beyer A, Parra I, Weigel NL, Herynk MH, Tsimelzon A, Lewis MT, Chamness GC, Hilsenbeck SG, Ando S, Fuqua SA. Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat 2010, 121:1-11. 10.1007/s10549-009-0436-8, 2995248, 19533338.
25. Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol 1993, 170:31-35. 10.1002/path.1711700106, 8100853.
26. Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 2006, 25:3994-4008. 10.1038/sj.onc.1209415, 16491124.
27. 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. 10.1002/ijc.2910520415, 1399140.
28. 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. 10.1007/s00428-005-0003-6, 16075292.
29. Panet-Raymond V, Gottlieb B, Beitel LK, Pinsky L, Trifiro MA. Interactions between androgen and estrogen receptors and the effects on their transactivational properties. Mol Cell Endocrinol 2000, 167:139-150. 10.1016/S0303-7207(00)00279-3, 11000528.
30. Bentel JM, Birrell SN, Pickering MA, Holds DJ, Horsfall DJ, Tilley WD. Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol 1999, 154:11-20. 10.1016/S0303-7207(99)00109-4, 10509795.
31. Bhattacharyya RS, Krishnan AV, Swami S, Feldman D. Fulvestrant (ICI 182,780) down-regulates androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells. Mol Cancer Ther 2006, 5:1539-1549.
32. Wasielewski M, Elstrodt F, Klijn JG, Berns EM, Schutte M. Thirteen new p53 gene mutants identified among 41 human breast cancer cell lines. Breast Cancer Res Treat 2006, 99:97-101. 10.1007/s10549-006-9186-z, 16541312.
33. She QB, Chandarlapaty S, Ye Q, Lobo J, Haskell KM, Leander KR, DeFeo-Jones D, Huber HE, Rosen N. Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling. PLoS ONE 2008, 3:e3065. 10.1371/journal.pone.0003065, 2516933, 18725974.
34. Abukhdeir AM, Blair BG, Brenner K, Karakas B, Konishi H, Lim J, Sahasranaman V, Huang Y, Keen J, Davidson N, Vitolo MI, Bachman KE, Park BH. Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells. Breast Cancer Res Treat 2006, 99:23-33. 10.1007/s10549-006-9177-0, 16541319.
35. Soule HD, Maloney TM, Wolman SR, Peterson WD, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 1990, 50:6075-6086.
36. Bachman KE, Blair BG, Brenner K, Bardelli A, Arena S, Zhou S, Hicks J, De Marzo AM, Argani P, Park BH. p21(WAF1/CIP1) Mediates the Growth Response to TGF-beta in Human Epithelial Cells. Cancer Biol Ther 2004, 3:221-225.
37. Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 1998, 273:18623-18632. 10.1074/jbc.273.29.18623, 9660836.
38. ImageJ. , http://rsb.info.nih.gov/ij/
39. Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL, Mills GB, Hennessy BT. Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 2009, 15:2472-2478. 10.1158/1078-0432.CCR-08-1763, 19276248.
40. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 2001, 61:3550-3555.
41. Albertson DG. Conflicting evidence on the frequency of ESR1 amplification in breast cancer. Nat Genet 2008, 40:821-822. 10.1038/ng0708-821, 18583976.
42. Liu W, Xie CC, Zhu Y, Li T, Sun J, Cheng Y, Ewing CM, Dalrymple S, Turner AR, Isaacs JT, Chang BL, Zheng SL, Isaacs WB, Xu J. Homozygous deletions and recurrent amplifications implicate new genes involved in prostate cancer. Neoplasia 2008, 10:897-907. 2481576, 18670647.
43. 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. 10.1023/A:1006304518750, 10832596.
44. Vendola K, Zhou J, Wang J, Bondy CA. Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod 1999, 14:2328-2332. 10.1093/humrep/14.9.2328, 10469704.
45. Yanase T, Fan W. Modification of androgen receptor function by IGF-1 signaling implications in the mechanism of refractory prostate carcinoma. Vitam Horm 2009, 80:649-666.
46. Lu S, Liu M, Epner DE, Tsai SY, Tsai MJ. Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Mol Endocrinol 1999, 13:376-384. 10.1210/me.13.3.376, 10076995.
47. Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J, Hood L, Lin B. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci USA 2002, 99:11890-11895. 10.1073/pnas.182376299, 129364, 12185249.
48. Bolton EC, So AY, Chaivorapol C, Haqq CM, Li H, Yamamoto KR. Cell- and gene-specific regulation of primary target genes by the androgen receptor. Genes Dev 2007, 21:2005-2017. 10.1101/gad.1564207, 1948856, 17699749.
49. von Bueren AO, Ma R, Schlumpf M, Lichtensteiger W. Salbutamol exhibits androgenic activity in vitro. Br J Sports Med 2007, 41:874-878. discussion 878, 10.1136/bjsm.2007.035162, 2658979, 17510230.
50. Blankvoort BM, de Groene EM, van Meeteren-Kreikamp AP, Witkamp RF, Rodenburg RJ, Aarts JM. Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor. Anal Biochem 2001, 298:93-102. 10.1006/abio.2001.5352, 11673900.
51. Ma R, Cotton B, Lichtensteiger W, Schlumpf M. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci 2003, 74:43-50. 10.1093/toxsci/kfg102, 12730620.
52. Chou JL, Fan Z, DeBlasio T, Koff A, Rosen N, Mendelsohn J. Constitutive overexpression of cyclin D1 in human breast epithelial cells does not prevent G1 arrest induced by deprivation of epidermal growth factor. Breast Cancer Res Treat 1999, 55:267-283. 10.1023/A:1006217413089, 10517171.
53. Zhu X, Li H, Liu JP, Funder JW. Androgen stimulates mitogen-activated protein kinase in human breast cancer cells. Mol Cell Endocrinol 1999, 152:199-206. 10.1016/S0303-7207(99)00031-3, 10432237.
54. Davidson NE, Gelmann EP, Lippman ME, Dickson RB. Epidermal growth factor receptor gene expression in estrogen receptor-positive and negative human breast cancer cell lines. Mol Endocrinol 1987, 1:216-223. 10.1210/mend-1-3-216, 3502607.
55. Fitzpatrick SL, LaChance MP, Schultz GS. Characterization of epidermal growth factor receptor and action on human breast cancer cells in culture. Cancer Res 1984, 44:3442-3447.
56. Ho-Kim MA, Tremblay RR, Dube JY. Binding of methyltrienolone to glucocorticoid receptors in rat muscle cytosol. Endocrinology 1981, 109:1418-1423. 10.1210/endo-109-5-1418, 6975208.
57. Sarkisian CJ, Keister BA, Stairs DB, Boxer RB, Moody SE, Chodosh LA. Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis. Nat Cell Biol 2007, 9:493-505. 10.1038/ncb1567, 17450133.
58. el-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994, 54:1169-1174.
59. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993, 75:817-825. 10.1016/0092-8674(93)90500-P, 8242752.
60. Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev 2004, 18:2699-2711. 10.1101/gad.1256504, 15545627.
61. Karakas B, Weeraratna AT, Abukhdeir AM, Konishi H, Gustin JP, Vitolo MI, Bachman KE, Park BH. p21 Gene knock Down Does Not Identify Genetic Effectors Seen with Gene Knock Out. Cancer Biol Ther 2007, 6:1025-1030. 10.4161/cbt.6.7.4202, 2667557, 17611398.
62. Abukhdeir AM, Park BH. P21 and p27: roles in carcinogenesis and drug resistance. Expert Rev Mol Med 2008, 10:e19. 2678956, 18590585.
63. Strickfaden SC, Winters MJ, Ben-Ari G, Lamson RE, Tyers M, Pryciak PM. A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway. Cell 2007, 128:519-531. 10.1016/j.cell.2006.12.032, 1847584, 17289571.
64. Higgins MJ, Beaver JA, Wong HY, Gustin JP, Lauring JD, Garay JP, Konishi H, Mohseni M, Wang GM, Cidado J, Jelovac D, Cosgrove DP, Tamaki A, Abukhdeir AM, Park BH. PIK3CA mutations and EGFR overexpression predict for lithium sensitivity in human breast epithelial cells. Cancer Biol Ther 2011, 11:35-44. 3047087, 21124076.