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The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer

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Abstract

AIB1 (amplified in breast cancer 1), also called SRC-3 and NCoA-3, is a member of the p160 nuclear receptor co-activator family and is considered an important oncogene in breast cancer. Increased AIB1 levels in human breast cancer have been correlated with poor clinical prognosis. Overexpression of AIB1 in conjunction with members of the epidermal growth factor receptor (EGF/HER) tyrosine kinase family, such as HER2, is associated with resistance to tamoxifen therapy and decreased disease-free survival. A number of functional studies in cell culture and in rodents indicate that AIB1 has a pleiotropic role in breast cancer. Initially AIB1 was shown to have a role in the estrogen-dependent proliferation of breast epithelial cells. However, AIB1 also affects the growth of hormone-independent breast cancer and AIB1 levels are limiting for IGF-1-, EGF- and heregulin-stimulated biological responses in breast cancer cells and consequently the PI3 K/Akt/mTOR and other EGFR/HER2 signaling pathways are controlled by changes in AIB1 protein levels. The cellular levels and activity of AIB1 are in turn regulated at the levels of transcription, mRNA stability, post-translational modification, and by a complex control of protein half life. In particular, AIB1 activity as well as its half-life is modulated through a number of post-translational modifications including serine, threonine and tyrosine phosphorylation via kinases that are components of multiple signal transduction pathways. This review summarizes the possible mechanisms of how dysregulation of AIB1 at multiple levels can lead to the initiation and progression of breast cancer as well as its role as a predictor of response to breast cancer therapy, and as a possible therapeutic target.

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References

  1. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (1997) AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277(5328):965–968. doi:10.1126/science.277.5328.965

    Article  PubMed  CAS  Google Scholar 

  2. Onate SA, Tsai SY, Tsai MJ, O’Malley BW (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270(5240):1354–1357. doi:10.1126/science.270.5240.1354

    Article  PubMed  CAS  Google Scholar 

  3. Voegel JJ, Heine MJ, Zechel C, Chambon P, Gronemeyer H (1996) TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J 15(14):3667–3675

    PubMed  CAS  Google Scholar 

  4. Suen CS, Berrodin TJ, Mastroeni R, Cheskis BJ, Lyttle CR, Frail DE (1998) A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity. J Biol Chem 273(42):27645–27653. doi:10.1074/jbc.273.42.27645

    Article  PubMed  CAS  Google Scholar 

  5. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 90:569–580. doi:10.1016/S0092-8674(00)80516-4

    Article  PubMed  CAS  Google Scholar 

  6. Li H, Gomes PJ, Chen JD (1997) RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc Natl Acad Sci USA 94:8479–8484. doi:10.1073/pnas.94.16.8479

    Article  PubMed  CAS  Google Scholar 

  7. Takeshita A, Cardona GR, Koibuchi N, Suen CS, Chin WW (1997) TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1. J Biol Chem 272(44):27629–27634. doi:10.1074/jbc.272.44.27629

    Article  PubMed  CAS  Google Scholar 

  8. Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 387:677–684. doi:10.1038/42652

    Article  PubMed  CAS  Google Scholar 

  9. Liao L, Kuang SQ, Yuan Y, Gonzalez SM, O’Malley BW, Xu J (2002) Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1. J Steroid Biochem Mol Biol 83(1–5):3–14

    Article  PubMed  CAS  Google Scholar 

  10. Louie MC, Zou JX, Rabinovich A, Chen HW (2004) ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Mol Cell Biol 24(12):5157–5171. doi:10.1128/MCB.24.12.5157-5171.2004

    Article  PubMed  CAS  Google Scholar 

  11. Yan J, Yu CT, Ozen M, Ittmann M, Tsai SY, Tsai MJ (2006) Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. Cancer Res 66(22):11039–11046. doi:10.1158/0008-5472.CAN-06-2442

    Article  PubMed  CAS  Google Scholar 

  12. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O’Malley BW (2002) Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol Cell Biol 22(10):3549–3561. doi:10.1128/MCB.22.10.3549-3561.2002

    Article  PubMed  CAS  Google Scholar 

  13. Arimura A, vn Peer M, Schroder AJ, Rothman PB (2004) The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6. J Biol Chem 279(30):31105–31112. doi:10.1074/jbc.M404428200

    Article  PubMed  CAS  Google Scholar 

  14. Clayton AL, Hazzalin CA, Mahadevan LC (2006) Enhanced histone acetylation and transcription: a dynamic perspective. Mol Cell 23(3):289–296. doi:10.1016/j.molcel.2006.06.017

    Article  PubMed  CAS  Google Scholar 

  15. Yu C, York B, Wang S, Feng Q, Xu J, O’Malley BW (2007) An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. Mol Cell 25(5):765–778. doi:10.1016/j.molcel.2007.01.025

    Article  PubMed  CAS  Google Scholar 

  16. Cuny M, Kramar A, Courjal F, Johannsdottir V, Iacopetta B, Fontaine H, Grenier J, Culine S, Theillet C (2000) Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations. Cancer Res 60(4):1077–1083

    PubMed  CAS  Google Scholar 

  17. Iwase H, Omoto Y, Toyama T, Yamashita H, Hara Y, Sugiura H, Zhang Z (2003) Clinical significance of AIB1 expression in human breast cancer. Breast Cancer Res Treat 80(3):339–345. doi:10.1023/A:1024916126532

    Article  PubMed  CAS  Google Scholar 

  18. Shibata A, Hayashi Y, Imai T, Funahashi H, Nakao A, Seo H (2001) Somatic gene alteration of AIB1 gene in patients with breast cancer. Endocr J 48(2):199–204. doi:10.1507/endocrj.48.199

    Article  PubMed  CAS  Google Scholar 

  19. Kirkegaard T, McGlynn LM, Campbell FM, Müller S, Tovey SM, Dunne B, Nielsen KV, Cooke TG, Bartlett JM (2007) Amplified in breast cancer 1 in human epidermal growth factor receptor—positive tumors of tamoxifen-treated breast cancer patients. Clin Cancer Res 13(5):1405–1411. doi:10.1158/1078-0432.CCR-06-1933

    Article  PubMed  CAS  Google Scholar 

  20. Ginestier C, Cervera N, Finetti P, Esteyries S, Esterni B, Adelaide J, Xerri L, Viens P, Jacquemier J, Charafe-Jauffret E et al (2006) Prognosis and gene expression profiling of 20q13-amplified breast cancers. Clin Cancer Res 12(15):4533–4544. doi:10.1158/1078-0432.CCR-05-2339

    Article  PubMed  CAS  Google Scholar 

  21. Bouras T, Southey MC, Venter DJ (2001) Overexpression of the steroid receptor coactivator AIB1 in breast cancer correlates with the absence of estrogen and progesterone receptors and positivity for p53 and HER2/neu. Cancer Res 61(3):903–907

    PubMed  CAS  Google Scholar 

  22. List HJ, Reiter R, Singh B, Wellstein A, Riegel AT (2001) Expression of the nuclear coactivator AIB1 in normal and malignant breast tissue. Breast Cancer Res Treat 68(1):21–28. doi:10.1023/A:1017910924390

    Article  PubMed  CAS  Google Scholar 

  23. Zhao C, Yasui K, Lee CJ, Kurioka H, Hosokawa Y, Oka T, Inazawa J (2003) Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. Cancer 98(1):18–23. doi:10.1002/cncr.11482

    Article  PubMed  CAS  Google Scholar 

  24. Harigopal M, Heymann J, Ghosh S, Anagnostou V, Camp RL, Rimm DL (2009) Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association wit patient outcome. Breast Cancer Res Treat 115(1):77–85. doi:10.1007/s10549-008-0063-9

    Article  PubMed  CAS  Google Scholar 

  25. Hudelist G, Czerwenka K, Kubista E, Marton E, Pischinger K, Singer CF (2003) Expression of sex steroid receptors and their co-factors in normal and malignant breast tissue: AIB1 is a carcinoma-specific co-activator. Breast Cancer Res Treat 78(2):193–204. doi:10.1023/A:1022930710850

    Article  PubMed  CAS  Google Scholar 

  26. Henke RT, Eun Kim S, Maitra A, Paik S, Wellstein A (2006) Expression analysis of mRNA in formalin-fixed, paraffin-embedded archival tissues by mRNA in situ hybridization. Methods 38(4):253–262. doi:10.1016/j.ymeth.2005.11.013

    Article  PubMed  CAS  Google Scholar 

  27. Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S (2006) X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 9(2):121–132. doi:10.1016/j.ccr.2006.01.013

    Article  PubMed  CAS  Google Scholar 

  28. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D et al (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24(29):4660–4671. doi:10.1038/sj.onc.1208561

    Article  PubMed  CAS  Google Scholar 

  29. Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H et al (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66(21):10292–10301. doi:10.1158/0008-5472.CAN-05-4414

    Article  PubMed  CAS  Google Scholar 

  30. van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347(25):1999–2009. doi:10.1056/NEJMoa021967

    Article  PubMed  Google Scholar 

  31. Iwase H (2003) Molecular action of the estrogen receptor and hormone dependency in breast cancer. Breast Cancer 10(2):89–96. doi:10.1007/BF02967632

    Article  PubMed  Google Scholar 

  32. Burwinkel B, Wirtenberger M, Klaes R, Schmutzler RK, Grzybowska E, Försti A, Frank B, Bermejo JL, Bugert P, Wappenschmidt B et al (2005) Association of NCOA3 polymorphisms with breast cancer risk. Clin Cancer Res 11(6):2169–2174. doi:10.1158/1078-0432.CCR-04-1621

    Article  PubMed  CAS  Google Scholar 

  33. Deng CX (2006) BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res 34(5):1416–1426. doi:10.1093/nar/gkl010

    Article  PubMed  CAS  Google Scholar 

  34. Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK, Daly MB, Narod SA, Brunet JS, Vesprini D et al (2001) Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Res 61(14):5420–5424

    PubMed  CAS  Google Scholar 

  35. Kadouri L, Kote-Jarai Z, Easton DF, Hubert A, Hamoudi R, Glaser B, Abeliovich D, Peretz T, Eeles RA (2004) Polyglutamine repeat length in the AIB1 gene modifies breast cancer susceptibility in BRCA1 carriers. Int J Cancer 108(3):399–403. doi:10.1002/ijc.11531

    Article  PubMed  CAS  Google Scholar 

  36. Hughes DJ, Ginolhac SM, Coupier I, Barjhoux L, Gaborieau V, Bressac-de-Paillerets B, Chompret A, Bignon YJ, Uhrhammer N, Lasset C et al (2005) Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. Int J Cancer 117(2):230–233. doi:10.1002/ijc.21176

    Article  PubMed  CAS  Google Scholar 

  37. Spurdle AB, Antoniou AC, Kelemen L, Holland H, Peock S, Cook MR, Smith PL, Greene MH, Simard J, Plourde M et al (2006) The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 15(1):76–79. doi:10.1158/1055-9965.EPI-05-0709

    Article  PubMed  CAS  Google Scholar 

  38. Li AJ, Lerner DL, Gapuzan ME, Karlan BY (2005) AIB1 polymorphisms predict aggressive ovarian cancer phenotype. Cancer Epidemiol Biomarkers Prev 14(12):2919–2922. doi:10.1158/1055-9965.EPI-05-0540

    Article  PubMed  CAS  Google Scholar 

  39. Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107(3):309–330. doi:10.1007/s10549-007-9556-1

    Article  PubMed  CAS  Google Scholar 

  40. Reiter R, Wellstein A, Riegel AT (2001) An isoform of the coactivator AIB1 that increases hormone and growth factor sensitivity is overexpressed in breast cancer. J Biol Chem 276(43):39736–39741. doi:10.1074/jbc.M104744200

    Article  PubMed  CAS  Google Scholar 

  41. Bautista S, Valles H, Walker RL, Anzick S, Zeillinger R, Meltzer P, Theillet C (1998) In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity. Clin Cancer Res 4(12):2925–2929

    PubMed  CAS  Google Scholar 

  42. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272

    PubMed  CAS  Google Scholar 

  43. List HJ, Lauritsen KJ, Reiter R, Powers C, Wellstein A, Riegel AT (2001) Ribozyme targeting demonstrates that the nuclear receptor coactivator AIB1 is a rate-limiting factor for estrogen-dependent growth of human MCF-7 breast cancer cells. J Biol Chem 276(26):23763–23768. doi:10.1074/jbc.M102397200

    Article  PubMed  CAS  Google Scholar 

  44. Jordan VC, Dowse LJ (1976) Tamoxifen as an anti-tumour agent: effect on oestrogen binding. J Endocrinol 68(02):297–303. doi:10.1677/joe.0.0680297

    Article  PubMed  CAS  Google Scholar 

  45. Osborne CK (1998) Tamoxifen in the treatment of breast cancer. N Engl J Med 339(22):1609–1618. doi:10.1056/NEJM199811263392207

    Article  PubMed  CAS  Google Scholar 

  46. Osborne CK, Shou J, Massarweh S, Schiff R (2005) Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin Cancer Res 11(2 Pt 2):865s–870s

    PubMed  CAS  Google Scholar 

  47. Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R (2003) Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 95(5):353–361

    PubMed  CAS  Google Scholar 

  48. Kirkegaard T, McGlynn LM, Campbell FM, Muller S, Tovey SM, Dunne B, Nielsen KV, Cooke TG, Bartlett JM (2007) Amplified in breast cancer 1 in human epidermal growth factor receptor—positive tumors of tamoxifen-treated breast cancer patients. Clin Cancer Res 13(5):1405–1411. doi:10.1158/1078-0432.CCR-06-1933

    Article  PubMed  CAS  Google Scholar 

  49. Dihge L, Bendahl PO, Grabau D, Isola J, Lovgren K, Ryden L, Ferno M (2007) Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer. Breast Cancer Res Treat 109(2):255–262. doi:10.1007/s10549-007-9645-1

    Article  PubMed  CAS  Google Scholar 

  50. Reiter R, Oh AS, Wellstein A, Riegel AT (2004) Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic ligands with different intrinsic activity. Oncogene 23(2):403–409. doi:10.1038/sj.onc.1207202

    Article  PubMed  CAS  Google Scholar 

  51. Silva CM, Shupnik MA (2007) Integration of steroid and growth factor pathways in breast cancer: focus on signal transducers and activators of transcription and their potential role in resistance. Mol Endocrinol 21(7):1499–1512. doi:10.1210/me.2007-0109

    Article  PubMed  CAS  Google Scholar 

  52. Fleming FJ, Myers E, Kelly G, Crotty TB, McDermott EW, O’Higgins NJ, Hill AD, Young LS (2004) Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1. J Clin Pathol 57(10):1069–1074. doi:10.1136/jcp.2004.016733

    Article  PubMed  CAS  Google Scholar 

  53. Massarweh S, Schiff R (2007) Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities. Clin Cancer Res 13(7):1950–1954. doi:10.1158/1078-0432.CCR-06-2540

    Article  PubMed  CAS  Google Scholar 

  54. Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R (2004) Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 96(12):926–935

    Article  PubMed  CAS  Google Scholar 

  55. Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, Jiang J, Howat WJ, Ali S, Carroll JS (2008) Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 456(7222):663–666. doi:10.1038/nature07483

    Article  PubMed  CAS  Google Scholar 

  56. Patel RR, Sharma CG, Jordan VC (2007) Optimizing the antihormonal treatment and prevention of breast cancer. Breast Cancer 14(2):113–122. doi:10.2325/jbcs.966

    Article  PubMed  Google Scholar 

  57. Lin NU, Winer EP (2008) Advances in adjuvant endocrine therapy for postmenopausal women. J Clin Oncol 26(5):798–805. doi:10.1200/JCO.2007.15.0946

    Article  PubMed  CAS  Google Scholar 

  58. Belosay A, Brodie AM, Njar VC (2006) Effects of novel retinoic acid metabolism blocking agent (VN/14–1) on letrozole-insensitive breast cancer cells. Cancer Res 66(23):11485–11493. doi:10.1158/0008-5472.CAN-06-2168

    Article  PubMed  CAS  Google Scholar 

  59. Shin I, Miller T, Arteaga CL (2006) ErbB receptor signaling and therapeutic resistance to aromatase inhibitors. Clin Cancer Res 12(3 Pt 2):1008s–1012s. doi:10.1158/1078-0432.CCR-05-2352

    Article  PubMed  CAS  Google Scholar 

  60. Lauritsen KJ, List HJ, Reiter R, Wellstein A, Riegel AT (2002) A role for TGF-beta in estrogen and retinoid mediated regulation of the nuclear receptor coactivator AIB1 in MCF-7 breast cancer cells. Oncogene 21(47):7147–7155. doi:10.1038/sj.onc.1205943

    Article  PubMed  CAS  Google Scholar 

  61. Louie MC, Revenko AS, Zou JX, Yao J, Chen HW (2006) Direct control of cell cycle gene expression by proto-oncogene product ACTR, and its autoregulation underlies its transforming activity. Mol Cell Biol 26(10):3810–3823. doi:10.1128/MCB.26.10.3810-3823.2006

    Article  PubMed  CAS  Google Scholar 

  62. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441(7092):431–436. doi:10.1038/nature04870

    Article  PubMed  CAS  Google Scholar 

  63. Liu Y, Lu C, Shen Q, Munoz-Medellin D, Kim H, Brown PH (2004) AP-1 blockade in breast cancer cells causes cell cycle arrest by suppressing G1 cyclin expression and reducing cyclin-dependent kinase activity. Oncogene 23(50):8238–8246. doi:10.1038/sj.onc.1207889

    Article  PubMed  CAS  Google Scholar 

  64. Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, Iglehart JD (2004) NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 101(27):10137–10142. doi:10.1073/pnas.0403621101

    Article  PubMed  CAS  Google Scholar 

  65. Singh S, Shi Q, Bailey ST, Palczewski MJ, Pardee AB, Iglehart JD, Biswas DK (2007) Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer. Mol Cancer Ther 6(7):1973–1982. doi:10.1158/1535-7163.MCT-07-0063

    Article  PubMed  CAS  Google Scholar 

  66. Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Richardson AL et al (2007) Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 129(6):1065–1079. doi:10.1016/j.cell.2007.03.052

    Article  PubMed  CAS  Google Scholar 

  67. Laviola L, Natalicchio A, Giorgino F (2007) The IGF-I signaling pathway. Curr Pharm Des 13(7):663–669. doi:10.2174/138161207780249146

    Article  PubMed  CAS  Google Scholar 

  68. Wang Z, Rose DW, Hermanson O, Liu F, Herman T, Wu W, Szeto D, Gleiberman A, Krones A, Pratt K et al (2000) Regulation of somatic growth by the p160 coactivator p/CIP. Proc Natl Acad Sci USA 97(25):13549–13554. doi:10.1073/pnas.260463097

    Article  PubMed  CAS  Google Scholar 

  69. Xu J, Liao L, Ning G, Yoshida-Komiya H, Deng C, O’Malley BW (2000) The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Proc Natl Acad Sci USA 97(12):6379–6384. doi:10.1073/pnas.120166297

    Article  PubMed  CAS  Google Scholar 

  70. Torres-Arzayus MI, De Mora JF, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR, Brown M (2004) High tumor incidence and activation of the PI3 K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 6(3):263–274. doi:10.1016/j.ccr.2004.06.027

    Article  PubMed  CAS  Google Scholar 

  71. Tilli MT, Reiter R, Oh AS, Henke RT, McDonnell K, Gallicano GI, Furth PA, Riegel AT (2005) Overexpression of an N-terminally truncated isoform of the nuclear receptor coactivator amplified in breast cancer 1 leads to altered proliferation of mammary epithelial cells in transgenic mice. Mol Endocrinol 19(3):644–656. doi:10.1210/me.2004-0106

    Article  PubMed  CAS  Google Scholar 

  72. Oh A, List HJ, Reiter R, Mani A, Zhang Y, Gehan E, Wellstein A, Riegel AT (2004) The nuclear receptor coactivator AIB1 mediates insulin-like growth factor I-induced phenotypic changes in human breast cancer cells. Cancer Res 64(22):8299–8308. doi:10.1158/0008-5472.CAN-04-0354

    Article  PubMed  CAS  Google Scholar 

  73. Torres-Arzayus MI, Yuan J, DellaGatta JL, Lane H, Kung AL, Brown M (2006) Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland. Cancer Res 66(23):11381–11388. doi:10.1158/0008-5472.CAN-06-2316

    Article  PubMed  CAS  Google Scholar 

  74. Kuang SQ, Liao L, Zhang H, Lee AV, O’Malley BW, Xu J (2004) AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Cancer Res 64(5):1875–1885. doi:10.1158/0008-5472.CAN-03-3745

    Article  PubMed  CAS  Google Scholar 

  75. Wu RC, Qin J, Yi P, Wong J, Tsai SY, Tsai MJ, O’Malley BW (2004) Selective Phosphorylations of the SRC-3/AIB1 Coactivator Integrate Genomic Reponses to Multiple Cellular Signaling Pathways. Mol Cell 15(6):937–949. doi:10.1016/j.molcel.2004.08.019

    Article  PubMed  CAS  Google Scholar 

  76. Olayioye MA, Neve RM, Lane HA, Hynes NE (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19(13):3159–3167. doi:10.1093/emboj/19.13.3159

    Article  PubMed  CAS  Google Scholar 

  77. Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354. doi:10.1038/nrc1609

    Article  PubMed  CAS  Google Scholar 

  78. Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, Booser D, Theriault RL, Buzdar AU, Dempsey PJ et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 24(26):4236–4244. doi:10.1200/JCO.2006.05.6861

    Article  PubMed  CAS  Google Scholar 

  79. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752. doi:10.1038/35021093

    Article  PubMed  CAS  Google Scholar 

  80. Bittner RM (2006) International Genomics Consortium expO dataset- breast samples. In: International Genomics Consortium. http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2109

  81. Fereshteh MP, Lahusen T, Kim SE, Xu J, O’Malley BW, Wellstein A, Furth PA, Riegel AT (2008) The nuclear receptor coactivator Amplified in Breast Cancer-1 is required for Neu (ErbB2/HER2) activation, signaling and mammary tumorigenesis in mice. Cancer Res 68(10):3697–3706. doi:10.1158/0008-5472.CAN-07-6702

    Article  PubMed  CAS  Google Scholar 

  82. Lahusen T, Fereshteh M, Oh A, Wellstein A, Riegel AT (2007) Epidermal growth factor receptor tyrosine phosphorylation and signaling controlled by a nuclear receptor coactivator, amplified in breast cancer 1. Cancer Res 67(15):7256–7265. doi:10.1158/0008-5472.CAN-07-1013

    Article  PubMed  CAS  Google Scholar 

  83. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182. doi:10.1126/science.3798106

    Article  PubMed  CAS  Google Scholar 

  84. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905):707–712. doi:10.1126/science.2470152

    Article  PubMed  CAS  Google Scholar 

  85. Nahta R, Esteva FJ (2007) Trastuzumab: triumphs and tribulations. Oncogene 26(25):3637–3643. doi:10.1038/sj.onc.1210379

    Article  PubMed  CAS  Google Scholar 

  86. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. doi:10.1056/NEJMoa052122

    Article  PubMed  CAS  Google Scholar 

  87. Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH et al (2005) Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23(16):3676–3685. doi:10.1200/JCO.2005.07.032

    Article  PubMed  CAS  Google Scholar 

  88. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672. doi:10.1056/NEJMoa052306

    Article  PubMed  CAS  Google Scholar 

  89. Nahta R, Esteva FJ (2006) Herceptin: mechanisms of action and resistance. Cancer Lett 232(2):123–138. doi:10.1016/j.canlet.2005.01.041

    Article  PubMed  CAS  Google Scholar 

  90. Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358(13):1409–1411. doi:10.1056/NEJMc0801440

    Article  PubMed  CAS  Google Scholar 

  91. Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M (2001) Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J Natl Cancer Inst 93(24):1852–1857. doi:10.1093/jnci/93.24.1852

    Article  PubMed  CAS  Google Scholar 

  92. Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ (2005) Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 65(23):11118–11128. doi:10.1158/0008-5472.CAN-04-3841

    Article  PubMed  CAS  Google Scholar 

  93. Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S, Arteaga CL (2002) Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res 62(14):4132–4141

    PubMed  CAS  Google Scholar 

  94. Le XF, Claret FX, Lammayot A, Tian L, Deshpande D, LaPushin R, Tari AM, Bast RC Jr (2003) The role of cyclin-dependent kinase inhibitor p27Kip1 in anti-HER2 antibody-induced G1 cell cycle arrest and tumor growth inhibition. J Biol Chem 278(26):23441–23450. doi:10.1074/jbc.M300848200

    Article  PubMed  CAS  Google Scholar 

  95. Nahta R, Takahashi T, Ueno NT, Hung MC, Esteva FJ (2004) P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer Res 64(11):3981–3986. doi:10.1158/0008-5472.CAN-03-3900

    Article  PubMed  CAS  Google Scholar 

  96. Anido J, Scaltriti M, Bech Serra JJ, Santiago Josefat B, Todo FR, Baselga J, Arribas J (2006) Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J 25(13):3234–3244. doi:10.1038/sj.emboj.7601191

    Article  PubMed  CAS  Google Scholar 

  97. Avivar A, Garcia-Macias MC, Ascaso E, Herrera G, O’Connor JE, de Mora JF (2006) Moderate overexpression of AIB1 triggers pre-neoplastic changes in mammary epithelium. FEBS Lett 580(22):5222–5226. doi:10.1016/j.febslet.2006.08.057

    Article  PubMed  CAS  Google Scholar 

  98. Mussi P, Yu C, O’Malley BW, Xu J (2006) Stimulation of steroid receptor coactivator-3 (SRC-3) gene overexpression by a positive regulatory loop of E2F1 and SRC-3. Mol Endocrinol 20(12):3105–3119. doi:10.1210/me.2005-0522

    Article  PubMed  CAS  Google Scholar 

  99. Cullen BR (2004) Transcription and processing of human microRNA precursors. Mol Cell 16(6):861–865. doi:10.1016/j.molcel.2004.12.002

    Article  PubMed  CAS  Google Scholar 

  100. Hossain A, Kuo MT, Saunders GF (2006) Mir-17–5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 26(21):8191–8201. doi:10.1128/MCB.00242-06

    Article  PubMed  CAS  Google Scholar 

  101. Lonard DM, O’Malley BW (2008) SRC-3 transcription-coupled activation, degradation, and the ubiquitin clock: is there enough coactivator to go around in cells? Sci Signal 1(13):pe16. doi:10.1126/stke.113pe16

    Article  PubMed  Google Scholar 

  102. Hoeller D, Hecker CM, Dikic I (2006) Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 6(10):776–788. doi:10.1038/nrc1994

    Article  PubMed  CAS  Google Scholar 

  103. Mani A, Oh AS, Bowden ET, Lahusen T, Lorick KL, Weissman AM, Schlegel R, Wellstein A, Riegel AT (2006) E6AP mediates regulated proteasomal degradation of the nuclear receptor coactivator amplified in breast cancer 1 in immortalized cells. Cancer Res 66(17):8680–8686. doi:10.1158/0008-5472.CAN-06-0557

    Article  PubMed  CAS  Google Scholar 

  104. Wu R, Feng Q, Lonard D, Omalley B (2007) SRC-3 Coactivator Functional Lifetime Is Regulated by a Phospho-Dependent Ubiquitin Time Clock. Cell 129(6):1125–1140. doi:10.1016/j.cell.2007.04.039

    Article  PubMed  CAS  Google Scholar 

  105. Naeem H, Cheng D, Zhao Q, Underhill C, Tini M, Bedford MT, Torchia J (2007) The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methylation. Mol Cell Biol 27(1):120–134. doi:10.1128/MCB.00815-06

    Article  PubMed  CAS  Google Scholar 

  106. Li X, Lonard DM, Jung SY, Malovannaya A, Feng Q, Qin J, Tsai SY, Tsai MJ, O’Malley BW (2006) The SRC-3/AIB1 coactivator is degraded in a ubiquitin- and ATP-independent manner by the REGgamma proteasome. Cell 124(2):381–392. doi:10.1016/j.cell.2005.11.037

    Article  PubMed  CAS  Google Scholar 

  107. Yi P (2008) Atypical Protein Kinase C Regulates Dual Pathways for Degradation of the Oncogenic Coactivator SRC-3/AIB1. Mol Cell 29(4):465–476. doi:10.1016/j.molcel.2007.12.030

    Article  PubMed  CAS  Google Scholar 

  108. Feng Q, Yi P, Wong J, O’Malley BW (2006) Signaling within a coactivator complex: methylation of SRC-3/AIB1 is a molecular switch for complex disassembly. Mol Cell Biol 26(21):7846–7857. doi:10.1128/MCB.00568-06

    Article  PubMed  CAS  Google Scholar 

  109. Wu H, Sun L, Zhang Y, Chen Y, Shi B, Li R, Wang Y, Liang J, Fan D, Wu G et al (2006) Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation. J Biol Chem 281(31):21848–21856. doi:10.1074/jbc.M603772200

    Article  PubMed  CAS  Google Scholar 

  110. Font de Mora J, Brown M (2000) AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor. Mol Cell Biol 20(14):5041–5047. doi:10.1128/MCB.20.14.5041-5047.2000

    Article  PubMed  CAS  Google Scholar 

  111. Park KJ, Krishnan V, O’Malley BW, Yamamoto Y, Gaynor RB (2005) Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell 18(1):71–82. doi:10.1016/j.molcel.2005.03.006

    Article  PubMed  CAS  Google Scholar 

  112. Oh AS, Lahusen JT, Chien CD, Fereshteh MP, Zhang X, Dakshanamurthy S, Xu J, Kagan BL, Wellstein A, Riegel AT (2008) Tyrosine phosphorylation of the nuclear receptor coactivator AIB1/SRC-3 is enhanced by Abl kinase and is required for its activity in cancer cells. Mol Cell Biol 28(21):6580–6593. doi:10.1128/MCB.00118-08

    Article  PubMed  CAS  Google Scholar 

  113. Jope RS, Johnson GV (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29(2):95–102. doi:10.1016/j.tibs.2003.12.004

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC, USA

    Tyler Lahusen, Ralf T. Henke, Benjamin L. Kagan, Anton Wellstein & Anna T. Riegel

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  1. Tyler Lahusen
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  2. Ralf T. Henke
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Correspondence to Anton Wellstein.

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Lahusen, T., Henke, R.T., Kagan, B.L. et al. The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer. Breast Cancer Res Treat 116, 225–237 (2009). https://doi.org/10.1007/s10549-009-0405-2

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