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Estrogens, regulation of p53 and breast cancer risk: a balancing act

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Abstract

The paradoxical effects of ovarian hormones in both the promotion and prevention of breast cancer have been debated for over 30 years. Genetic studies have demonstrated that ovarian hormones act through NF-κB to stimulate proliferation and ductal elongation, whereas the p53 tumor suppressor protein plays a central role in rendering the mammary epithelium resistant to tumorigenesis. Transcriptional profiles now suggest that ovarian hormones stimulate a constellation of genes that interact with NF-κB and p53 to arbitrate the competing demands for proliferation and surveillance. Genes that participate in chromatin remodeling are among the acute transcriptional responses to estrogens and progestins. These genes are proposed to initiate epigenetic programs that influence the balance between proliferation and surveillance, and render the breast epithelium resistant to tumors.

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References

  1. Singletary SE (2003) Rating the risk factors for breast cancer. Ann Surg 237:474–482

    Article  PubMed  Google Scholar 

  2. Eliassen AH, Missmer SA, Tworoger SS, Spiegelman D, Barbieri RL, Dowsett M, Hankinson SE (2006) Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst 98:1406–1415

    Article  CAS  PubMed  Google Scholar 

  3. Cavalieri E, Chakravarti D, Guttenplan J, Hart E, Ingle J, Jankowiak R, Muti P, Rogan E, Russo J, Santen R, Sutter T (2006) Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta 1766:63–78

    CAS  PubMed  Google Scholar 

  4. Frech MS, Halama ED, Tilli MT, Singh B, Gunther EJ, Chodosh LA, Flaws JA, Furth PA (2005) Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Res 65:681–685

    CAS  PubMed  Google Scholar 

  5. Montero GG, Vanzulli SI, Cerliani JP, Bottino MC, Bolado J, Vela J, Becu-Villalobos D, Benavides F, Gutkind S, Patel V, Molinolo A, Lanari C (2007) Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment. Breast Cancer Res 9:R22

    Article  CAS  Google Scholar 

  6. Aupperlee MD, Drolet AA, Durairaj S, Wang W, Schwartz RC, Haslam SZ (2008) Strain-specific differences in the mechanisms of progesterone regulation of murine mammary gland development. Endocrinology

  7. Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO (2009) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41:324–328

    Article  CAS  PubMed  Google Scholar 

  8. Tchatchou S, Jung A, Hemminki K, Sutter C, Wappenschmidt B, Bugert P, Weber BH, Niederacher D, Arnold N, Varon-Mateeva R, Ditsch N, Meindl A, Schmutzler RK, Bartram CR, Burwinkel B (2009) A variant affecting a putative miRNA target site in estrogen receptor (ESR) 1 is associated with breast cancer risk in premenopausal women. Carcinogenesis 30:59–64

    Article  CAS  PubMed  Google Scholar 

  9. Maguire P, Margolin S, Skoglund J, Sun XF, Gustafsson JA, Borresen-Dale AL, Lindblom A (2005) Estrogen receptor beta (ESR2) polymorphisms in familial and sporadic breast cancer. Breast Cancer Res Treat 94:145–152

    Article  CAS  PubMed  Google Scholar 

  10. MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S (1970) Age at first birth and breast cancer risk. Bull World Health Organ 43:209–221

    CAS  PubMed  Google Scholar 

  11. Rosner B, Colditz GA, Willett WC (1994) Reproductive risk factors in a prospective study of breast cancer: the Nurses’ Health Study. Am J Epidemiol 139:819–835

    CAS  PubMed  Google Scholar 

  12. Grubbs CJ, Farnell DR, Hill DL, McDonough KC (1985) Chemoprevention of N-nitroso-N-methylurea-induced mammary cancers by pretreatment with 17 beta-estradiol and progesterone. J Natl Cancer Inst 74:927–931

    CAS  PubMed  Google Scholar 

  13. Sivaraman L, Stephens LC, Markaverich BM, Clark JA, Krnacik S, Conneely OM, O’Malley BW, Medina D (1998) Hormone-induced refractoriness to mammary carcinogenesis in Wistar–Furth rats. Carcinogenesis 19:1573–1581

    Article  CAS  PubMed  Google Scholar 

  14. Cabanes A, Wang M, Olivo S, deAssis S, Gustafsson JA, Khan G, Hilakivi-Clarke L (2004) Prepubertal estradiol and genistein exposures up-regulate BRCA1 mRNA and reduce mammary tumorigenesis. Carcinogenesis 25:741–748

    Article  CAS  PubMed  Google Scholar 

  15. Birch JM, Alston RD, McNally RJ, Evans DG, Kelsey AM, Harris M, Eden OB, Varley JM (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628

    Article  CAS  PubMed  Google Scholar 

  16. Nichols KE, Malkin D, Garber JE, Fraumeni JF Jr, Li FP (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomarkers Prev 10:83–87

    CAS  PubMed  Google Scholar 

  17. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M (2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28:622–629

    Article  CAS  PubMed  Google Scholar 

  18. Crook T, Brooks LA, Crossland S, Osin P, Barker KT, Waller J, Philp E, Smith PD, Yulug I, Peto J, Parker G, Allday MJ, Crompton MR, Gusterson BA (1998) p53 mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours. Oncogene 17:1681–1689

    Article  CAS  PubMed  Google Scholar 

  19. Xu X, Wagner K-U, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A, Deng C-X (1999) Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumor formation. Nat Genet 22:37–43

    Article  CAS  PubMed  Google Scholar 

  20. Meijers-Heijboer H, Van Den OA, Klijn J, Wasielewski M, De Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, Veghel-Plandsoen M, Elstrodt F, Van Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton DF, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Narod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber BL, Rahman N, Stratton MR (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31:55–59

    Article  CAS  PubMed  Google Scholar 

  21. Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119:591–602

    Article  CAS  PubMed  Google Scholar 

  22. Dunphy KA, Blackburn AC, Yan H, O’Connell LR, Jerry DJ (2008) Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53± mice. Breast Cancer Res 10:R43

    Article  PubMed  CAS  Google Scholar 

  23. Jerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, Butel JS, Medina D (2000) A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene 19:1052–1058

    Article  CAS  PubMed  Google Scholar 

  24. Medina D, Kittrell FS (2003) p53 function is required for hormone-mediated protection of mouse mammary tumorigenesis. Cancer Res 63:6140–6143

    CAS  PubMed  Google Scholar 

  25. Becker KA, Lu S, Dickinson ES, Dunphy KA, Mathews L, Schneider SS, Jerry DJ (2005) Estrogen and progesterone regulate radiation-induced p53 activity in mammary epithelium through TGF-beta-dependent pathways. Oncogene 24:6345–6353

    CAS  PubMed  Google Scholar 

  26. Lu S, Becker KA, Hagen MJ, Yan H, Roberts AL, Mathews LA, Schneider SS, Siegelmann HT, Macbeth KJ, Tirrell SM, Blanchard JL, Jerry DJ (2008) Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology 149:4809–4820

    Article  CAS  PubMed  Google Scholar 

  27. Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV, Karin M (2001) IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell 107:763–775

    Article  CAS  PubMed  Google Scholar 

  28. Demicco EG, Kavanagh KT, Romieu-Mourez R, Wang X, Shin SR, Landesman-Bollag E, Seldin DC, Sonenshein GE (2005) RelB/p52 NF-kappaB complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor IkappaB-alpha expression and promote carcinogenesis of the mammary gland. Mol Cell Biol 25:10136–10147

    Article  CAS  PubMed  Google Scholar 

  29. Mallepell S, Krust A, Chambon P, Brisken C (2006) Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci USA 103:2196–2201

    Article  CAS  PubMed  Google Scholar 

  30. Feng Y, Manka D, Wagner KU, Khan SA (2007) Estrogen receptor-alpha expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice. Proc Natl Acad Sci USA 104:14718–14723

    Article  CAS  PubMed  Google Scholar 

  31. Minter LM, Dickinson ES, Naber SP, Jerry DJ (2002) Epithelial cell cycling predicts p53 responsiveness to gamma-irradiation during post-natal mammary gland development. Development 129:2997–3008

    CAS  PubMed  Google Scholar 

  32. Sivaraman L, Conneely OM, Medina D, O’Malley BW (2001) p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis. Proc Natl Acad Sci USA 98:12379–12384

    Article  CAS  PubMed  Google Scholar 

  33. Chapman NR, Perkins ND (2000) Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1. J Biol Chem 275:4719–4725

    Article  CAS  PubMed  Google Scholar 

  34. Krones-Herzig A, Adamson E, Mercola D (2003) Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence. Proc Natl Acad Sci USA 100:3233–3238

    Article  CAS  PubMed  Google Scholar 

  35. Krones-Herzig A, Mittal S, Yule K, Liang H, English C, Urcis R, Soni T, Adamson ED, Mercola D (2005) Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res 65:5133–5143

    Article  CAS  PubMed  Google Scholar 

  36. Ewan KB, Shyamala G, Ravani SA, Tang Y, Akhurst R, Wakefield L, Barcellos-Hoff MH (2002) Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation. Am J Pathol 160:2081–2093

    CAS  PubMed  Google Scholar 

  37. Ewan KB, Oketch-Rabah HA, Ravani SA, Shyamala G, Moses HL, Barcellos-Hoff MH (2005) Proliferation of estrogen receptor-alpha-positive mammary epithelial cells is restrained by transforming growth factor-beta1 in adult mice. Am J Pathol 167:409–417

    CAS  PubMed  Google Scholar 

  38. Ewan KB, Henshall-Powell RL, Ravani SA, Pajares MJ, Arteaga C, Warters R, Akhurst RJ, Barcellos-Hoff MH (2002) Transforming growth factor-beta1 mediates cellular response to DNA damage in situ. Cancer Res 62:5627–5631

    CAS  PubMed  Google Scholar 

  39. An W, Kim J, Roeder RG (2004) Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell 117:735–748

    Article  CAS  PubMed  Google Scholar 

  40. Weaver IC, D’Alessio AC, Brown SE, Hellstrom IC, Dymov S, Sharma S, Szyf M, Meaney MJ (2007) The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J Neurosci 27:1756–1768

    Article  CAS  PubMed  Google Scholar 

  41. Robinson GE, Fernald RD, Clayton DF (2008) Genes and social behavior. Science 322:896–900

    Article  CAS  PubMed  Google Scholar 

  42. D’Cruz CM, Moody SE, Master SR, Hartman JL, Keiper EA, Imielinski MB, Cox JD, Wang JY, Ha SI, Keister BA, Chodosh LA (2002) Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland. Mol Endocrinol 16:2034–2051

    Article  PubMed  CAS  Google Scholar 

  43. Wilkinson DS, Tsai WW, Schumacher MA, Barton MC (2008) Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. Mol Cell Biol 28:1988–1998

    Article  CAS  PubMed  Google Scholar 

  44. Pena PV, Hom RA, Hung T, Lin H, Kuo AJ, Wong RP, Subach OM, Champagne KS, Zhao R, Verkhusha VV, Li G, Gozani O, Kutateladze TG (2008) Histone H3K4me3 binding is required for the DNA repair and apoptotic activities of ING1 tumor suppressor. J Mol Biol 380:303–312

    Article  CAS  PubMed  Google Scholar 

  45. Ythier D, Larrieu D, Brambilla C, Brambilla E, Pedeux R (2008) The new tumor suppressor genes ING: genomic structure and status in cancer. Int J Cancer 123:1483–1490

    Article  CAS  PubMed  Google Scholar 

  46. Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA (2009) Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA 302:774–780

    Article  CAS  PubMed  Google Scholar 

  47. Lonning PE, Taylor PD, Anker G, Iddon J, Wie L, Jorgensen LM, Mella O, Howell A (2001) High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy. Breast Cancer Res Treat 67:111–116

    Article  CAS  PubMed  Google Scholar 

  48. Rajkumar L, Guzman RC, Yang J, Thordarson G, Talamantes F, Nandi S (2001) Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis. Proc Natl Acad Sci USA 98:11755–11759

    Article  CAS  PubMed  Google Scholar 

  49. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870

    Article  CAS  PubMed  Google Scholar 

  50. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der BB, Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252–4263

    Article  CAS  PubMed  Google Scholar 

  51. Pettersson K, Grandien K, Kuiper GG, Gustafsson JA (1997) Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Mol Endocrinol 11:1486–1496

    Article  CAS  PubMed  Google Scholar 

  52. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS (1997) Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 277:1508–1510

    Article  CAS  PubMed  Google Scholar 

  53. Kass L, Durando M, Ramos JG, Varayoud J, Powell CE, Luque EH, Munoz-de-Toro M (2004) Association of increased estrogen receptor beta2 expression with parity-induced alterations in the rat mammary gland. J Steroid Biochem Mol Biol 91:29–39

    Article  CAS  PubMed  Google Scholar 

  54. Liu W, Konduri SD, Bansal S, Nayak BK, Rajasekaran SA, Karuppayil SM, Rajasekaran AK, Das GM (2006) Estrogen receptor-alpha binds p53 tumor suppressor protein directly and represses its function. J Biol Chem 281:9837–9840

    Article  CAS  PubMed  Google Scholar 

  55. Liu G, Schwartz JA, Brooks SC (2000) Estrogen receptor protects p53 from deactivation by human double minute-2. Cancer Res 60:1810–1814

    CAS  PubMed  Google Scholar 

  56. Akaogi K, Nakajima Y, Ito I, Kawasaki S, Oie SH, Murayama A, Kimura K, Yanagisawa J (2009) KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERalpha. Oncogene 28:2894–2902

    Article  CAS  PubMed  Google Scholar 

  57. Shirley SH, Rundhaug JE, Tian J, Cullinan-Ammann N, Lambertz I, Conti CJ, Fuchs-Young R (2009) Transcriptional regulation of estrogen receptor-alpha by p53 in human breast cancer cells. Cancer Res 69:3405–3414

    Article  CAS  PubMed  Google Scholar 

  58. Pilat MJ, Christman JK, Brooks SC (1996) Characterization of the estrogen receptor transfected MCF10A breast cell line 139B6. Breast Cancer Res Treat 37:253–266

    Article  CAS  PubMed  Google Scholar 

  59. Zhang J, Tu Y, Smith-Schneider S (2005) Activation of p53, inhibition of telomerase activity and induction of estrogen receptor beta are associated with the anti-growth effects of combination of ovarian hormones and retinoids in immortalized human mammary epithelial cells. Cancer Cell Int 5:6

    Article  PubMed  CAS  Google Scholar 

  60. Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431

    Article  CAS  PubMed  Google Scholar 

  61. Menendez D, Inga A, Resnick MA (2009) The expanding universe of p53 targets. Nat Rev Cancer 9:724–737

    Article  CAS  PubMed  Google Scholar 

  62. Lewandowski SA, Thiery J, Jalil A, Leclercq G, Szczylik C, Chouaib S (2005) Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity. Oncogene 24:4789–4798

    Article  CAS  PubMed  Google Scholar 

  63. Paruthiyil S, Parmar H, Kerekatte V, Cunha GR, Firestone GL, Leitman DC (2004) Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Res 64:423–428

    Article  CAS  PubMed  Google Scholar 

  64. Behrens D, Gill JH, Fichtner I (2007) Loss of tumourigenicity of stably ERbeta-transfected MCF-7 breast cancer cells. Mol Cell Endocrinol 274:19–29

    Article  CAS  PubMed  Google Scholar 

  65. Hartman J, Lindberg K, Morani A, Inzunza J, Strom A, Gustafsson JA (2006) Estrogen receptor beta inhibits angiogenesis and growth of T47D breast cancer xenografts. Cancer Res 66:11207–11213

    Article  CAS  PubMed  Google Scholar 

  66. Sotoca AM, van den BH, Vervoort J, van der SP, Strom A, Gustafsson JA, Rietjens I, Murk AJ (2008) Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells. Toxicol Sci 105:303–311

    Article  PubMed  CAS  Google Scholar 

  67. Hodges-Gallagher L, Valentine CD, El BS, Kushner PJ (2008) Estrogen receptor beta increases the efficacy of antiestrogens by effects on apoptosis and cell cycling in breast cancer cells. Breast Cancer Res Treat 109:241–250

    Article  CAS  PubMed  Google Scholar 

  68. Chang EC, Charn TH, Park SH, Helferich WG, Komm B, Katzenellenbogen JA, Katzenellenbogen BS (2008) Estrogen receptors alpha and beta as determinants of gene expression: influence of ligand, dose, and chromatin binding. Mol Endocrinol 22:1032–1043

    Article  CAS  PubMed  Google Scholar 

  69. Liu Y, Gao H, Marstrand TT, Strom A, Valen E, Sandelin A, Gustafsson JA, Dahlman-Wright K (2008) The genome landscape of ERalpha- and ERbeta-binding DNA regions. Proc Natl Acad Sci USA 105:2604–2609

    Article  CAS  PubMed  Google Scholar 

  70. Chang EC, Frasor J, Komm B, Katzenellenbogen BS (2006) Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells. Endocrinology 147:4831–4842

    Article  CAS  PubMed  Google Scholar 

  71. Lin CY, Strom A, Li KS, Kietz S, Thomsen JS, Tee JB, Vega VB, Miller LD, Smeds J, Bergh J, Gustafsson JA, Liu ET (2007) Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer. Breast Cancer Res 9:R25

    Article  PubMed  CAS  Google Scholar 

  72. Secreto FJ, Monroe DG, Dutta S, Ingle JN, Spelsberg TC (2007) Estrogen receptor alpha/beta isoforms, but not betacx, modulate unique patterns of gene expression and cell proliferation in Hs578T cells. J Cell Biochem 101:1125–1147

    Article  CAS  PubMed  Google Scholar 

  73. Williams C, Edvardsson K, Lewandowski SA, Strom A, Gustafsson JA (2008) A genome-wide study of the repressive effects of estrogen receptor beta on estrogen receptor alpha signaling in breast cancer cells. Oncogene 27:1019–1032

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Institutes of Health (R01-CA095164, R01-CA105452 and R01-ES015739 DJJ).

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  1. Paige Laboratory, Department of Veterinary and Animal Sciences, University of Massachusetts, 161 Holdsworth Way, Amherst, MA, 01003-9286, USA

    D. Joseph Jerry, Karen A. Dunphy & Mary J. Hagen

  2. Pioneer Valley Life Sciences Institute, Springfield, MA, USA

    D. Joseph Jerry, Karen A. Dunphy & Mary J. Hagen

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  1. D. Joseph Jerry
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Correspondence to D. Joseph Jerry.

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Jerry, D.J., Dunphy, K.A. & Hagen, M.J. Estrogens, regulation of p53 and breast cancer risk: a balancing act. Cell. Mol. Life Sci. 67, 1017–1023 (2010). https://doi.org/10.1007/s00018-009-0244-7

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