Zentralbl Gynakol 2005; 127(4): 228-234
DOI: 10.1055/s-2005-836563
Übersicht

© Georg Thieme Verlag Stuttgart · New York

Östrogenrezeptor-β-Isoformen -Funktionen und klinische Bedeutung bei Brustkrebs

Estrogen Receptor β Isoforms - Functions and Clinical Relevance in Breast CancerD. Mitter1 , O. Ortmann1 , O. Treeck1
  • 1Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg, Caritas Krankenhaus St. Josef, Regensburg, Deutschland
Further Information

Publication History

Publication Date:
22 July 2005 (online)

Zusammenfassung

Östrogenrezeptoren (ER) sind ligandenregulierte Transkriptionsfaktoren, die eine zelluläre Reaktion auf Östrogene vermitteln. Bisher konnten die zwei ER-Typen ERα und ERβ identifiziert werden. ERα besitzt eine wesentliche Bedeutung als prädiktiver Faktor für die Wirksamkeit einer endokrinen Therapie des Mammakarzinoms. Patientinnen, deren Tumoren ERα exprimieren, erhalten eine adjuvante endokrine Therapie. Neuere Untersuchungen liefern Hinweise für eine entscheidende Bedeutung von ERβ und seinen Isoformen für die Prognose von Brustkrebserkrankungen. In dieser Übersicht wird der aktuelle Kenntnisstand zur Funktion von ERβ und seinen Subtypen zusammengefasst.

Abstract

Estrogen receptors (ER) are hormone regulated transcription factors which mediate the cellular estrogen response. So far two types of ER could be identified, ERα and ERβ. ERα plays an important role as a predictive factor for the effectiveness of endocrine agents in the treatment of breast cancer. Patients with ERα positive tumors receive adjuvant endocrine therapy. Recent findings indicate a crucial role of ERβ and its isoforms for the prognosis of breast cancer. This paper reviews the current knowledge on the functions of ERβ and its splice variants.

Literatur

  • 1 Barettino D, Vivanco Ruiz M M, Stunnenberg H G. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor.  EMBO Journal. 1994;  13 3039-3049
  • 2 Beatson G. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases.  Lancet. 1896;  II 104-107
  • 3 Beekman J M, Allan G F, Tsai S Y, Tsai M -J, O'Malley B W. Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain.  Mol Endocrinol. 1993;  7 1266-1274
  • 4 Bhat R A, Harnish D C, Stevis P E. A novel human estrogen receptor β: Identification and functional analysis of additional N-terminal amino acids.  J Steroid Biochem Molec Biol. 1998;  67 233-240
  • 5 Bieche I, Parfait B, Laurendeau I. Quantification of estrogen receptor α and β expression in sporadic breast cancer.  Oncogene. 2001;  20 8109-8115
  • 6 Bord S, Horner S, Beavans S, Compston J. Estrogen receptors α and β are differentially expressed in developing human bone.  J Clin Endocrinol Metab. 2001;  86 2309-2314
  • 7 Boyd M, Hildebrandt R H, Bartow S A. Expression of the estrogen receptor gene in developing and adult human breast.  Breast Cancer Res and Treat. 1996;  37 243-251
  • 8 Braidman I P, Hainey L, Batra G. Localisation of estrogen receptor beta protein expression in adult human bone.  J Bone Miner Res. 2001;  16 214-220
  • 9 Cardenas H, Burke K A, Bigsby R M, Pope W F, Nephew K P. Estrogen receptor beta in sheep ovary during the estrous cycle and early pregnancy.  Biol Reprod. 2001;  65 128-134
  • 10 Chen F P, Hsu T, Hu C H, Wang W D, Wang K C, Teng L F. Expression of estrogen receptors alpha and beta in human osteoblasts: identification of exon-2 deletion variant of estrogen receptor beta in postmenopausal women.  Chang Gung Med J. 2004;  27 107-115
  • 11 Cheng G, Weihua Z, Warner M, Gustafsson J A. Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland.  Proc Natl Acad Sci USA. 2004;  101 3739-3746
  • 12 Chi A, Chen X, Chirala M, Younes M. Differential expression of estrogen receptor beta isoforms in human breast cancer tissue.  Anticancer Research. 2003;  23 211-216
  • 13 Collins P, Webb C. Estrogen hits the surface.  Nature Med. 1999;  5 1130-1131
  • 14 Couse J F, Korach K S. Estrogen receptor null mice: what have we learned and where will they lead us?.  Endocr Rev. 1999;  20 358-417
  • 15 Couse J F, Curtis Hewitt S, Korach K S. Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissue.  J Steroid Biochem Mol Biol. 2000;  74 287-296
  • 16 Crandall D L, Busler D E, Novak T J, Weber R V, Kral J G. Identification of estrogen receptor β RNA in human breast and abdominal subcutaneous adipose tissue.  Biochem Biophys Res Com. 1998;  248 523-526
  • 17 Cullen R, Maguire T M, McDermott E W. Studies on oestrogen receptor-α and -β mRNA in human breast cancer.  Eur J Cancer. 2001;  37 1118-1122
  • 18 DeCremoux P, Tran-Perennou C, Brockdorff B L. Validation of real-time PCR for analysis of human breast cancer cell lines resistant or sensitive to treatment with antioestrogens.  Endocrine Relat Cancer. 2003;  10 409-418
  • 19 Dotzlaw H, Leygue E, Watson P H, Murphy L C. Expression of estrogen receptor β in human breast tumors.  J Clin Endo Metab. 1997;  82 2371-2374
  • 20 Dotzlaw H, Leygue E, Watson P H, Murphy L C. Estrogen receptor β messenger RNA expression in human breast tumor biopsies: relationship to steroid receptor status and regulation by progestin.  Cancer Res. 1999;  59 529-532
  • 21 Durand B, Saunders M, Gaudon C, Roy B, Losson R, Chambon P. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.  EMBO Journal. 1994;  13 5370-5382
  • 22 Egner U, Heinrich N, Ruff M, Gangloff M, Mueller-Fahrnow A, Wurtz J M. Different ligands, different receptor conformations: modelling of the hER alpha LBD in complex with agonists and antagonists.  Medical Research Reviews. 2001;  21 523-539
  • 23 Enmark E, Pelto-Huikko M, Grandien K. Human estrogen receptor β-Gene structure, chromosomal localisation and expression pattern.  J Cli Endo Metab. 1997;  82 4258-4265
  • 24 Esslimani-Sahla M, Simony-Lafontaine J, Kramar A, Lavaill R, Mollevi C, Warner M, Gustafsson J A, Rochefort H. Estrogen receptor beta (ER beta) level but not its ER beta cx variant helps to predict tamoxifen resistance in breast cancer.  Clin Cancer. 2004;  10 5769-5776
  • 25 Evans R M. The steroid and thyroid hormone receptor superfamily.  Science. 1988;  240 889-895
  • 26 Fawell S E, Lees J A, White R, Parker M G. Characterisation and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor.  Cell. 1990;  60 953-962
  • 27 Forman B M, Samuels H H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model.  Mol Endocrinol. 1990;  4 1293-1301
  • 28 Fritsch M, Leary C M, Furlow J D, Ahrens H, Schuh T J, Mueller G C, Gorski J. A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain.  Biochemistry. 1992;  31 5303-5311
  • 29 Fujimoto J, Sun W S, Misao R, Sakaguchi H, Aoki I, Toyoki H, Tamaya T. Expression of estrogen receptor beta exon-deleted variant mRNAs in ovary and uterine endometrium.  J Steroid Biochem Mol Biol. 2003;  84 133-140
  • 30 Fuqua S AW, Schiff R, Parra I, Moore J T, Mohsin S K, Osborne C K, Clark G M, Allred D C. Estrogen Receptor β Protein in Human Breast Cancer: Correlation with Clinical Tumor Parameters.  Cancer Res. 2003;  63 2434-2439
  • 31 Gosden J R, Middleton P G, Rout D. Localization of the human oestrogen receptor gene to chromosome 6q24-q27 by in situ hybridization.  Cytogenet Cell Genet. 1986;  43 218-220
  • 32 Green S, Chambon P. Nuclear Receptors enhance our understanding of transcription regulation.  Trends Genet. 1988;  4 309-314
  • 33 Green S, Chambon P. Nuclear Hormone Receptor: from perception to mechanism. In: Parker MG (ed). Nuclear Hormone Receptors. Academic Press Ltd., San Diego, CA 1991; 15-38
  • 34 Hanstein B, Liu H, Yancisin M C, Brown M. Functional analysis of a novel estrogen receptor-β isoform.  Mol Endocrinol. 1999;  13 129-137
  • 35 Harper M J, Walpole A L. A new derivative of triphenylethylene: effect on implantation and mode of action in rats.  J Reprod Fertility. 1967;  13 101-119
  • 36 Henke B R, Consoler T G, Go N, Hale R L, Hohman D R, Johnes S A. A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta.  J Med Chem. 2002;  45 5492-5505
  • 37 Hopp T A, Weiss H L, Parra I S, Cui Y, Osborne C K, Fuqua S A. Low Levels of Estrogen Receptor β Protein Predict Resistance to Tamoxifen Therapy in Breast Cancer.  Clin Cancer Res. 2004;  10 7490-7499
  • 38 Inoue S, Ogawa S, Horie K, Hoshino S, Goto W, Hosoi T, Tsutsumi O, Muramatusu M, Oouchi Y. An estrogen receptor beta isoform that lacks exon 5 has dominant negative activity on both ERalpha and ERbeta.  Biochem Biophys Res Commun. 2000;  279 814-819
  • 39 Iwao K, Miyoshi Y, Egawa C. Quantitative analysis of estrogen receptor-β mRNA and its variants in human breast cancers.  Int J Cancer. 2000 a;  88 733-736
  • 40 Iwao K, Miyoshi Y, Egawa C. Quantitative analysis of estrogen receptor-α and -β messenger RNA expression in breast carcinoma by real-time polymerase chain reaction.  Cancer. 2000 b;  89 1732-1738
  • 41 Jarvinen T A, Pelto-Huikko M, Holli K, Isola J. Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer.  Am J Pathol. 2000;  156 29-35
  • 42 Jensen E V, Jacobson H I. Basic guides to the mechanism of estrogen action.  Recent Prog Horm Res. 1962;  18 387-414
  • 43 Jensen E V, Suzuki T, Kawashima T, Stumpf W E, Jungblut P W, DeSombre E R. A two-step mechanism for the interaction of estradiol with rat uterus.  PNAS. 1968;  59 632-638
  • 44 Jensen E V, Cheng G, Palmieri C. Estrogen receptors and proliferation markers in primary and recurrent breast cancer.  Proc natl Acad Sci USA. 2001;  98 15197-15202
  • 45 Johnston S R, Haynes B P, Smith I E. et al . Acquired Tamoxifen resistance in human breast cancer and reduced intra-tumoral drug concentration.  Lancet. 1993;  342 1521-1522
  • 46 Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.  Science. 1995;  270 1491-1494
  • 47 Kelley S T, Thackray V G. Phylogenetic analyses reveal ancient duplication of estrogen receptor isoforms.  J Molec Evol. 1999;  49 609-614
  • 48 Kim K, Thu N, Faville B, Safe S. Domains of estrogen receptor alpha (Er alpha) required for Eralpha/Sp1-mediated activation of GC-rich promoters by estrogens and anti-estrogens in breast cancer cells.  Mol Endocrinol. 2003;  17 804-817
  • 49 Knowlden J M, Gee J MW, Robertson J FR. A possible divergent role for the oestrogen receptor alpha and beta subtypes in clinical breast cancer.  Int J Cancer. 2000;  89 209-212
  • 50 Korach K S. Estrogen receptor knock-out mice: molecular and endocrine phenotypes.  J Soc Gynaecol Invest. 2000;  7 S 16-S 17
  • 51 Krege J H, Hodin J B, Couse J F, Enmark E, Warner M, Mahler J F, Sar M, Korach K S, Gustafsson J A, Smithies O. Generation and reproductive phenotypes of mice lacking estrogen receptor beta.  PNAS. 1998;  95 5925-5930
  • 52 Kuiper G G, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J A. Cloning of a novel receptor expressed in rat prostate and ovary.  PNAS. 1997;  93 5925-5930
  • 53 Kuiper G G, Carlsson B, Grandine K. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptor α and β.  Endocrinology. 1997;  138 863-870
  • 54 Kumar V, Green S, Staub A, Chambon P. Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor.  EMBO J. 1986;  5 2231-2236
  • 55 Kumar V, Green S, Stack G, Berry M, Jin J R, Chambon P. Functional domains of the human estrogen receptor.  Cell. 1987;  51 941-951
  • 56 Kurebayashi J, Otsuki T, Kunisue H. Expression levels of estrogen receptor-α, estrogen receptor-β, coactivators, and corepressors in breast cancer.  Clin Cancer Res. 2000;  6 512-518
  • 57 LaVoie H A, DeSimone D C, Gillio-Meina C, Hui Y Y. Cloning and characterization of porcine ovarian estrogen receptor beta isoforms.  Biol Reprod. 2002;  66 616-623
  • 58 Lees J A, Fawell S E, Parker M G. Identification of constitutive and steroid-dependent transactivation domains in the mouse oestrogen receptor.  J Steroid Biochem. 1989;  34 33-39
  • 59 Lewandowski S, Kalita K, Kaczmarek L. Estrogen receptor β: potential functional significance of a variety of mRNA isoforms.  FEBS Lett. 2002;  524 1-5
  • 60 Leygue E, Dotslaw H, Watson P H, Murphy L C. Altered estrogen receptor α and β messenger RNA expression during human breast tumorigenesis.  Cancer Res. 1998;  58 3197-3201
  • 61 Leygue E, Dotslaw H, Watson P H, Murphy L C. Expression of estrogen receptor β 1, β 1 and β 5 messenger RNAs in human breast tissue.  Cancer Res. 1999;  59 1175-1179
  • 62 Locker G Y. Hormonal therapy of breast cancer.  Cancer Treat Rev. 1998;  24 221-240
  • 63 Mann S, Laucirica R, Carlson N. Estrogen receptor beta expression in invasive breast cancer.  Hum Pathol. 2001;  32 113-118
  • 64 Metzger N J, Ali S, Bornert J M, Chambon P. Characterisation of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells.  J Biol Chem. 1995;  270 9535-9542
  • 65 Miyoshi Y, Taguchi T, Gustafsson J A, Noguchi S. Clinicopathological characteristica of estrogen receptor beta positive human breast cancer.  Jpn J Cancer Res. 2001;  92 1057-1061
  • 66 Murphy L C, Leygue E, Niu Y, Snel L, Ho S M, Watson P H. Relationship of coregulator and estrogen receptor isoform expression to de novo tamoxifen resistance in human breast cancer.  British J of Cancer. 2002;  87 1411-1416
  • 67 Muss H B. Endocrine therapy for advanced breast cancer: a review.  Breast Cancer Res Treat. 1992;  21 15-26
  • 68 Montano M M, Muller V, Trobaugh A, Katzenellenbogen B S. The carboxy-terminal F domain of the human estrogen receptor: role in the transcriptional activity of the receptor and the effectiveness of anti-estrogens as estrogen antagonists.  Mol Endocrinol. 1995;  9 814-825
  • 69 Mosselman S, Polman J, Dijkema R. ER-β: identification and characterisation of a novel human estrogen receptor.  FEBS Lett. 1996;  392 49-53
  • 70 Ogawa S, Inoune S, Watanabe T. The complete primary structure of human estrogen receptor β (hERβ) and its heterodimerisation with ERα in vivo and in vitro.  Biochem Biophys Res Comm. 1998 a;  243 22-126
  • 71 Ogawa S, Inoune S, Watanabe T. Molecular cloning and characterisation of human estrogen receptor βcx: a potential inhibitor of estrogen action in human.  Nucleic Acids Res. 1998;  26 3505-3512
  • 72 Ogawa S, Chan J, Chester A E, Gustafsson J A, Korach K S, Pfaff D W. Survival of reproductive behaviours in estrogen receptor beta gene-deficient (beta ERKO) male and female mice.  PNAS. 1999;  96 12887-12892
  • 73 O'Neil P A, Davies M PA, Shaaban A M, Innes H, Torevell A, Sibson D R, Foster C S. Wild-type oestrogen receptor beta (ERβI) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers.  Br J Cancer. 2004;  91 1694-1702
  • 74 Omoto Y, Inoue S, Ogawa S. Clinical value of the wild-type estrogen receptor β expression in breast cancer.  Cancer Lett. 2001;  163 207-212
  • 75 Omoto Y, Kobayashi S, Inoue S. Evaluation of oestrogen receptor β wild-type and variant protein expression and relationship with clinicopathological factors in breast cancers.  Eur J Cancer. 2002;  38 380-386
  • 76 Osborne C K, Bardou V, Hopp T A, Chamness G C, Hilsenbeck S G, Fuqua S A, Wong J, Allred D C, Clark G M, Schiff R. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in Tamoxifen resistance in breast cancer.  J Nat Cancer Inst.. 2003;  95 353-361
  • 77 Pace P, Taylor J, Suntharalingam S. Human estrogen receptor β binds DNA in a manner similar to and dimerises with estrogen receptor α.  J Biol Chem. 1997;  272 25832-25838
  • 78 Palmieri C, Cheng G J, Saji S. Estrogen receptor beta in breast cancer.  Endocr Relat Cancer. 2002;  9 1-13
  • 79 Palmieri C, Saji S, Sakaguchi H, Cheng G, Sunters A, O'Hare M J, Warmer M, Gustafsson J A, Coombes R C, Lam E WF. The expression of estrogen receptor (ER)-β and its variants, but not ERα, in adult human mammary fibroblasts.  J Mol Endocrinol. 2004;  33 35-50
  • 80 Park B W, Kim K S, Heo M K. Expression of estrogen receptor-β in normal mammary and tumor tissues: is it protective in breast carcinogenesis?.  Breast Cancer Res Treat. 2003;  80 79-85
  • 81 Parmar H, Young P, Emerman J T, Neve R M, Dairkee S, Cunha G R. A novel method for growing human breast epithelium in vivo using mouse and human mammary fibroblasts.  Endocrinol. 2002;  143 4886-4896
  • 82 Peng B, Lu B, Leygue E, Murphy L C. Putative functional characteristics of human estrogen receptor beta isoforms.  J Mol Endocrinol. 2003;  30 13-29
  • 83 Petersen D N, Tkalcevic G T, Koza-Taylor P H, Turi T G, Brown T A. Identification of estrogen receptor β 2, a functional variant of estrogen receptor β expressed in normal rat tissues.  Endocrinology. 1998;  139 1082-1092
  • 84 Pettersson K, Delaunay F, Gustafsson J A. Estrogen receptor β acts as a dominant regulator of estrogen signalling.  Oncogene. 2000;  19 4970-4978
  • 85 Picard D, Salser S J, Yamamoto K R. A movable and regulable inactivation function within the steroid domain of the glucocorticoid receptor.  Cell. 1988;  54 1073-1080
  • 86 Pietras R, Szego C M. Specific binding sites for oestrogen at the outer surface of isolated endometrial cells.  Nature. 1977;  265 69-72
  • 87 Poola I, Abraham J, Liu A. Estrogen receptor beta splice variant mRNAs are differentially altered during breast carcinogenesis.  J Steroid Biochem Molec Biol. 2002;  82 169-179
  • 88 Poola I, Abraham J, Baldwin K. Identification of ten exon deleted mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor β mRNA is distinct from that of estrogen receptor α.  FEBS Lett. 2002 b;  516 133-138
  • 89 Pratt W B, Jolly D J, Pratt D V, Hollenberg S M, Giguere Y, Cadepond F M. A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.  J Biol Chem. 1988;  263 267-272
  • 90 Pratt W B. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor.  J Biol Chem. 1993;  268 21455-21458
  • 91 Price R H, Lorenzon N, Handa R J. Differential expression of estrogen receptor beta splice variants in rat bran: identification and characterization of a novel variant missing exon 4.  Brain Res Mol Brain Res. 2000;  80 260-268
  • 92 Price R H, Butler C A, Webb P, Uht R, Kushner P, Handa R J. A Splice Variant of Estrogen Receptor β Missing Exon 3 Displays Altered Subnuclear Localization and Capacity for Transcriptional Activation.  Endocrinology. 2001;  142 2039-2049
  • 93 Razandi M, Pedram A, Greene G L, Levin E R. Cell membrane and nuclear estrogen receptors originate from a single transcript: studies of ERα and Erβ expressed in Chinese hamster ovary cells.  Molec Endo. 1999;  13 307-319
  • 94 Roger P, Sahla M E, Makela S. Decreased expression of estrogen receptor β protein in proliverative preinvasive mammary tumours.  Cancer Res. 2001;  61 2537-2541
  • 95 Saji S, Omoto Y, Shimizu C. Expression of estrogen receptor (ER)βcx protein in ERα-positive breast cancer; specific correlation with progesterone receptor.  Cancer Res. 2002;  62 4849-4853
  • 96 Sasano H, Suzuki T, Matsuzaki Y. Messenger ribonucleic acid in situ hybridisation analysis of estrogen receptors α and β in human breast carcinoma.  J Clin Endocrinol Metab. 1999;  84 781-785
  • 97 Saunders P TK, Millar M R, Williams K. Differential expression of estrogen receptor-α and -β and androgen receptor in the ovaries of marmosets and humans.  Biol Rep. 2000;  63 1098-2005
  • 98 Saunders P TK, Millar M R, Williams K. Expression of oestrogen receptor beta (Erβ 1) protein human breast cancer biopsies.  Br J Cancer. 2002;  86 250-256
  • 99 Scott G K, Kushner P, Vigne J L, Benz C C. Truncated forms of DNA-binding estrogen receptors in human breast cancer.  Clin Invest. 1991;  88 700-706
  • 100 Shaw J A, Udokang K, Mosquera J M. Oestrogen receptors alpha and beta in normal human breast carcinomas.  J Pathol. 2002;  198 450-457
  • 101 Skliris G P, Carder P J, Lansdown M RJ, Speirs V. Immunohistochemical detection of Erβ in breast cancer: towards more detailed receptor profiling?.  Br J Cancer. 2001;  84 1095-1098
  • 102 Skliris G P, Parkes A T, Limer J L. Evaluation of seven oestrogen receptor β antibodies for immunhistochemistry, Western blotting and flow cytometry in human breast tissue.  J Pathol. 2002;  197 155-162
  • 103 Skliris G P, Nunot K, Bell S M. Reduced expression of oestrogen receptor β in invasive breast cancer and its re-expression using DNA methyltransferase inhibitors in a cell line model.  J Pathol. 2003;  201 213-220
  • 104 Speirs V, Malone C, Walton D S, Kerin M J, Atkin S L. Increased expression of estrogen receptor β mRNA in tamoxifen-resistant breast cancer patients.  Cancer Res. 1999 a;  59 5421-5424
  • 105 Speirs V, Parkes A T, Kerin M J. Co-expression of estrogen receptor-α and -β: Poor prognostic factors in human breast cancer?.  Cancer Res. 1999 b;  59 525-528
  • 106 Speirs V, Adams I P, Walton D S, Atkins S L. Identification of wild-type and exon 5 deletion variants of estrogen receptor beta in normal human mammary gland.  J Clin Endocrinol Metab. 2000;  85 1601-1605
  • 107 Speirs V, Skliris G P, Burdall S E, Carder P J. Distinct expression patterns of Erα and Erβ in normal human mammary gland.  J Clin Path. 2002;  55 317-374
  • 108 Taylor A H, Al-Azzawi F. Immunolocalisation of oestrogen receptor beta in human tissue.  J Mol Endocrinol. 2000;  24 145-155
  • 109 Toft D, Gorski J. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterisation.  Proc Natl Acad Sci USA. 1999;  55 157-181
  • 110 Tong D, Schuster E, Seifert M. et al . Expression of estrogen receptor beta isoforms in human breast cancer tissues and cell lines.  Breast Cancer Res Treat. 2002;  71 249-255
  • 111 Tora L, White J, Brou C, Tasset D, Webster N, Scheer E. The human estrogen receptor has two independent nonacidic transcriptional activation functions.  Cell. 1998;  59 477-487
  • 112 Tremblay G B, Tremblay A, Copeland N G, Gilbert D J, Jenkins N A, Labrie F. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta.  Molr Endocrinol. 1997;  11 49-53
  • 113 Vladusic E A, Hornby A E, Guerra-Vladusic F K, Lupu R. Expression of Estrogen Receptor β Messenger RNA Variant in Breast Cancer.  Cancer Res. 1998;  58 210-214
  • 114 Walther N, Lioutas C, Tillmann G, Ivell R. Cloning of bovine estrogen receptor beta (ERbeta): expression of novel deleted isoforms in reproductive tissue.  Mol Cell Endocrinol. 1999;  152 37-45
  • 115 Webster N J, Green S, Jin J R, Chambon P. The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function.  Cell. 1988;  54 199-207
  • 116 Wilkinson H A, Dahllund J, Liu H. Identification and characterisation of a functionally form of human estrogen receptor β.  Endocrinology. 2002;  143 1558-1561
  • 117 Xu L, Pan-Hammarstrom Q, Forsti A, Hemminki K, Hammarstrom L, Labuda D, Gustafsson J A, Dahlman-Wright K. Human estrogen receptor beta 548 is not a common variant in three distinct populations.  Endocrinol. 2003;  144 3541-3546
  • 118 Yamishita S. Localisation and functions of steroid hormone receptors.  Histol Histopathol. 1998;  13 255-270
  • 119 Zhao C, Taylor J, Suntharalingam S. Human estrogen receptor β binds DNA in a manner similar to and dimerises with estrogen receptor α.  J Biol Chem. 1997;  272 25832-25838
  • 120 Zhao C, Lam E W, Sunters A, Enmark E, De Bella M T, Coombes R C, Gustafsson J A, Dahlman-Wright K. Expression of estrogen receptor beta isoforms in normal breast epithelial cells and breast cancer: regulation by methylation.  Oncogene. 2003;  22 7600-7606

Dr. O Treeck

Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg · Caritas Krankenhaus St. Josef

Landshuter Str. 66

93053 Regensburg

Phone: 09 41/782 75 20

Fax: 09 41/782 75 15

Email: otreeck@caritasstjosef.de