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A role for TGF-β in estrogen and retinoid mediated regulation of the nuclear receptor coactivator AIB1 in MCF-7 breast cancer cells

Oncogene volume 21, pages 7147–7155 (2002)Cite this article

Abstract

AIB1 (amplified in breast cancer 1) is a nuclear receptor coactivator gene amplified and overexpressed in breast cancer. However, the mechanisms by which AIB1 is regulated are unclear. Here we show that 17β-estradiol represses AIB1 mRNA and protein expression in MCF-7 human breast cancer cells primarily by suppressing AIB1 gene transcription. Estrogen levels present in fetal calf serum are sufficient to maintain AIB1 mRNA and protein at low basal levels, and this repression is reversed by the addition of antiestrogens or all-trans retinoic acid. Interestingly, cycloheximide inhibition experiments revealed that secondary protein synthesis was necessary to induce AIB1 expression by antiestrogens and retinoids. Experiments with TGF-β and TGF-β blocking antibodies demonstrated that this growth factor modulates AIB1 expression and showed that the antiestrogen and retinoid induction of AIB1 gene expression is mediated at least in part through TGF-β. These data reveal a mechanism of estrogen-induced down-modulation of the overall hormone sensitivity of cells through feedback inhibition of coactivator gene expression. These data also suggest that antiestrogens can shift the sensitivity of cells to non-estrogenic proliferative signaling by increasing cellular levels of AIB1. This effect may play a role in breast cancer progression and resistance to drug treatment.

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References

  • Akiyama N, Matsuo Y, Sai H, Noda M, Kizaka-Kondoh S . 2000 Mol. Cell. Biol. 20: 3266–3273

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

  • Bai J, Uehara Y, Montell DJ . 2001 Cell 103: 1047–1058

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

  • Belandia B, Parker MG . 2000 J. Biol. Chem. 275: 30801–30805

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

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

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

  • Choudhury A, Singh RK, Moniaux N, El-Metwally TH, Aubert JP, Batra SK . 2000 J. Biol. Chem. 275: 33929–33936

  • Degitz SJ, Morris D, Foley GL, Francis BM . 1998 Teratology 58: 197–204

  • Dumont N, Arteaga CL . 2000 Breast Cancer Res. 2: 125–132

  • Farina AR, Coppa A, Tiberio A, Tacconelli A, Turco A, Colletta G, Gulino A, Mackay AR . 1998 Int. J. Cancer 75: 721–730

  • Ghadimi BM, Schrock E, Walker RL, Wangsa D, Jauho A, Meltzer PS, Ried T . 1999 Am. J. Pathol. 154: 525–536

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

  • Jakowlew SB, Zakowicz H, Moody TW . 2000 Peptides 21: 1831–1837

  • Karey KP, Sirbasku DA . 1988 Cancer Res. 48: 4083–4092

  • Knabbe C, Lippman ME, Wakefield LM, Flanders KC, Kasid A, Derynck R, Dickson RB . 1987 Cell 48: 417–428

  • Koli KM, Ramsey TT, Ko Y, Dugger TC, Brattain MG, Arteaga CL . 1997 J. Biol. Chem. 272: 8296–8302

  • Lee S-K, Kim H-J, Kim JW, Lee JW . 1999 Mol. Endocrinol. 13: 1924–1933

  • Li H, Chen JD . 1998 J. Biol. Chem. 273: 5948–5954

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

  • Lippman ME, Bolan G . 1975 Nature 256: 592–593

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

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

  • McKenna NJ, Lanz RB, O'Malley BW . 1999 Endocrine Rev. 20: 321–344

  • McKenna NJ, O'Malley BW . 2002 Cell 108: 465–474

  • Misiti S, Schomburg L, Yen PM, Chin WW . 1998 Endocrinology 139: 2493–2500

  • Nephew KP, Ray S, Hlaing M, Ahluwalia A, Wu SD, Long X, Hyder SM, Bigsby RM . 2000 Biol. Reprod. 63: 361–367

  • Oft M, Heider KH, Beug H . 1998 Curr. Biol. 8: 1243–1252

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

  • Orlando V, Strutt H, Paro R . 1997 Methods 11: 205–214

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

  • Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, Masuda K, Kimura A, Nakamura Y, Inazawa J, Abe T, Yamagishi H . 2000 Int. J. Cancer 89: 217–223

  • Segars JH, Marks MS, Hirschfeld S, Driggers PH, Martinez E, Grippo JF, Wahli W, Ozato K . 1993 Mol. Cell. Biol. 13: 2258–2268

  • Suen C-S, Berrodin TJ, Mastroeni R, Cheskis BJ, Lyttle CR, Frail DE . 1998 J. Biol. Chem. 273: 27645–27653

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

  • Vindelov LL, Christensen IJ, Nissen NI . 1983 Cytometry 3: 323–327

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

  • Walfish PG, Yoganathan T, Yang Y-F, Hong H, Butt TR, Stallcup MR . 1997 Proc. Natl. Acad. Sci. USA 94: 3697–3702

  • Wang D, Sun L, Zborowska E, Willson JK, Gong J, Verraraghavan J, Brattain MG . 1999 J. Biol. Chem. 274: 12840–12847

  • Wang Z, Rose DW, Hermanson O, Liu F, Herman T, Wu W, Szeto D, Gleiberman A, Krones A, Pratt K, Rosenfeld R, Glass CK, Rosenfeld MG . 2000 Proc. Natl. Acad. Sci. USA 97: 13549–13554

  • Welch DR, Fabra A, Nakajima M . 1990 Proc. Natl. Acad. Sci. USA 87: 7678–7682

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

  • Yue J, Mulder KM . 2000 J. Biol. Chem. 275: 30765–30773

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Acknowledgements

We thank Dr Ronald W Evans for the generous gift of the plasmid pRCMX-ACTR/A38. This work was supported by grants from the Breast Cancer Research Program of the Department of Defense, DAMD # 17-01-1-0249 (KJ Lauritsen) and DAMD # 17-99-1-9203 (AT Riegel).

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Authors and Affiliations

  1. Department of Oncology, Vincent T Lombardi Cancer Center, Research Building, E307, Georgetown University, 3970 Reservoir Road, Washington, 20007, DC, USA

    Kristina J Lauritsen, Heinz-Joachim List, Ronald Reiter, Anton Wellstein & Anna T Riegel

  2. Department of Pharmacology, Vincent T Lombardi Cancer Center, Research Building, E307, Georgetown University, 3970 Reservoir Road, Washington, 20007, DC, USA

    Anton Wellstein & Anna T Riegel

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  1. Kristina J Lauritsen
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Correspondence to Anna T Riegel.

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Lauritsen, K., List, HJ., Reiter, R. et al. A role for TGF-β in estrogen and retinoid mediated regulation of the nuclear receptor coactivator AIB1 in MCF-7 breast cancer cells. Oncogene 21, 7147–7155 (2002). https://doi.org/10.1038/sj.onc.1205943

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