Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Δ3 on estrogenic ligands with different intrinsic activity

Oncogene volume 23, pages 403–409 (2004)Cite this article

Abstract

The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) and its more active isoform AIB1-Δ3 are overexpressed in breast cancer and preneoplastic breast tissue. However, the impact of these proteins on the transcriptional activity of natural estrogens or selective estrogen receptor modulators (SERMs) has not been determined. Here we show that AIB1-Δ3 causes a significant increase in the efficacy of 17β-estradiol at both estrogen receptor-α (ER-α) and ER-β in ovarian, breast and endometrial cancer cell lines. AIB1-Δ3 also significantly increased the efficacy of the natural estrogen genistein at both ER-α and ER-β, whereas AIB1 had no effect on either the potency or efficacy of genistein at either receptor. The estrogenic efficacy of the partial agonist tamoxifen was significantly increased in all cell lines at ER-α by overexpression of AIB1-Δ3 both on transfected and endogenous estrogen responsive genes. In contrast, overexpression of AIB1 or AIB1-Δ3 had no effect on the potency or efficacy of the SERM raloxifene. We conclude that overexpression of the AIB1-Δ3 isoform will increase the estrogenicity of a variety of natural and pharmacologic compounds in tissues that develop hormone-dependent neoplasias and overexpression of these cofactors may be a contributing factor to the hormone-driven development of neoplasia and to antiestrogen resistance of breast cancers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM and Meltzer PS . (1997). Science, 277, 965–968.

  • Aravind L and Ponting CP . (1997). Curr. Biol., 7, 674–677.

  • Augereau P, Miralles F, Cavailles V, Gaudelet C, Parker M and Rochefort H . (1994). Mol. Endocrinol., 8, 693–703.

  • Bautista S, Valles H, Walker SL, Anzick S, Zellinger R, Meltzer P and Theillet C . (1998). Clin. Cancer Res., 4, 2925–2929.

  • Bouras T, Southey MC and Venter DJ . (2001). Cancer Res., 61, 903–907.

  • Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y and Evans RM . (1997). Cell, 90, 569–580.

  • Couse JF, Lindzey J, Grandien K, Gustafsson JA and Korach KS . (1997). Endocrinology, 138, 4613–4621.

  • Fan C-M and Crews ST . (1999). Curr Opin. Genet. Dev., 9, 580–587.

  • Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL and Cronin WM . (1994). J. Natl. Cancer Inst., 86, 527–537.

  • Glass CK and Rosenfeld MG . (2000). Genes Dev., 14, 121–141.

  • Guan XY, Xu J, Anzick SL, Zhang H, Trent JM and Meltzer PS . (1996). Cancer Res., 56, 3446–3450.

  • Hall JM and McDonnell DP . (1999). Endocrinology, 140, 5566–5578.

  • Jordan VC . (2002). Cancer Cell, 1, 215–217.

  • Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S and Gustafsson JA . (1997). Endocrinology, 138, 863–870.

  • Kurebayashi J, Otsuki T, Kunisue H, Tanaka K, Yamamoto S and Sonoo H . (2000). Clin Cancer Res., 6, 512–518.

  • Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R and Elgavish A . (2002). J. Nutr., 132, 552S–558S.

  • Leo C and Chen JD . (2000). Gene, 245, 1–11.

  • Li H, Gomes PJ and Chen JD . (1997). Proc. Natl. Acad. Sci. USA, 94, 8479–8484.

  • List HJ, Lauritsen KJ, Reiter R, Powers C, Wellstein A and Riegel AT . (2001a). J. Biol. Chem., 276, 23763–23768.

  • List HJ, Reiter R, Singh B, Wellstein A and Riegel AT . (2001b). Breast Cancer Res. Treat., 68, 21–28.

  • Liu H, Park W-J, Bentrem DJ, McKian KP, De Los Reyes A, Loweth JA, Schafer JM, Zapf JW and Jordan VC . 2002. J. Biol. Chem., 277, 9189–9198.

  • McKenna NJ, Lanz RB and O'Malley BW . (1999). Endocr. Rev., 20, 321–344.

  • Murphy LC, Simon SL, Parkes A, Leygue E, Dotzlaw H, Snell L, Troup S, Adeyinka A and Watson PH . (2000). Cancer Res., 60, 6266–6271.

  • Nilsson S and Gustafsson JA . (2002). Crit. Rev. Biochem. Mol. Biol., 37, 1–28.

  • Onate SA, Tsai SY, Tsai M-J and O'Malley BW . (1995). Science, 270, 1354–1357.

  • Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM and Schiff R . (2003). J. Natl. Cancer Inst., 95, 353–361.

  • Paige LA, Christensen DJ, Gron H, Norris JD, Gottlin EB, Padilla KM, Chang CY, Ballas LM, Hamilton PT, McDonnell DP and Fowlkes DM . (1999). Proc. Natl. Acad. Sci. USA, 96, 3999–4004.

  • Reiter R, Wellstein A and Riegel AT . (2001). J. Biol. Chem., 276, 39736–39741.

  • Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P and Rochefort H . (2001). Cancer Res., 61, 2537–2541.

  • Shang Y and Brown M . (2002). Science, 295, 2465–2468.

  • Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA and Greene GL . (1998). Cell, 95, 927–937.

  • Suen CS, Berrodin TJ, Mastroeni R, Cheskis BJ, Lyttle CR and Frail DE . (1998). J. Biol. Chem., 273, 27645–27653.

  • Szapary D, Huang Y and Simons Jr SS . (1999). Mol. Endocrinol., 13, 2108–2121.

  • Takeshita A, Cardona GR, Koibuchi N, Suen CS and Chin WW . (1997). J. Biol. Chem., 272, 27629–27634.

  • Tikkanen MK, Carter DJ, Harris AM, Le HM, Azorsa DO, Meltzer PS and Murdoch FE . (2000). Proc. Natl. Acad. Sci. USA, 97, 12536–12540.

  • Voegel JJ, Heine MJS, Zechel C, Chambon P and Gronmeyer H . (1996). EMBO J., 15, 3667–3675.

  • Watanabe T, Inoue S, Hiroi H, Orimo A, Kawashima H and Muramatsu M . (1998). Mol. Cell. Biol., 18, 442–449.

  • Xu J, Liao L, Ning G, Yoshida-Komiya H, Deng C and O'Malley BW . (2000). Proc. Natl. Acad. Sci. USA, 97, 6379–6384.

  • Zava DT and Duwe G . (1997). Nutr. Cancer, 27, 31–40.

Download references

Acknowledgements

The authors thank Dr Kristina J Lauritsen for her erudite assistance with editing this manuscript. This work was supported by grants from the Breast Cancer Research Program of the Department of Defense awarded to ATR (DAMD17-99-1-9203), AO (DAMD17-02-1-0394) and with developmental funds from the Lombardi Cancer Center's SPORE in Breast Cancer (P50 CA58185) awarded to ATR.

Author information

Authors and Affiliations

  1. Department of Oncology, Lombardi Cancer Center, Washington, 20057, DC, USA

    Ronald Reiter, Annabell S Oh, Anton Wellstein & Anna Tate Riegel

  2. Department of Pharmacology, Georgetown University, Washington, 20057, DC, USA

    Anton Wellstein & Anna Tate Riegel

Authors
  1. Ronald Reiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annabell S Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anton Wellstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Tate Riegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Tate Riegel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reiter, R., Oh, A., Wellstein, A. et al. Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Δ3 on estrogenic ligands with different intrinsic activity. Oncogene 23, 403–409 (2004). https://doi.org/10.1038/sj.onc.1207202

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207202

Keywords

This article is cited by

Search

Advanced search

Quick links