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Molecular Oncology Group (G.B.T., A.T., V.G.) Royal Victoria
Hospital Montréal, Québec, Canada H3A 1A1
Departments of Biochemistry, Medicine, and Oncology (V.G.)
McGill University Montréal, Québec, Canada
Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.)
ABL-Basic Research Program National Cancer Institute-Frederick
Cancer Research and Development Center Frederick, Maryland
21702
Laboratory of Molecular Endocrinology (F.L.) Centre
Hospitalier de l’Université Laval Research Center Ste-Foy,
Québec, Canada G1V 4G2
Estrogen receptor ß (ERß) is a novel steroid
receptor that is expressed in rat prostate and ovary. We have cloned
the mouse homolog of ERß and mapped the gene, designated
Estrb, to the central region of chromosome 12. The cDNA
encodes a protein of 485 amino acids that shares, respectively, 97%
and 60% identity with the DNA- and ligand-binding domains of mouse (m)
ER
. Mouse ERß binds to an inverted repeat spaced by three
nucleotides in a gel mobility shift assay and transactivates promoters
containing synthetic or natural estrogen response elements in an
estradiol (E2)-dependent manner. Scatchard
analysis indicates that mERß has slightly lower affinity for
E2 [dissociation constant
(Kd) = 0.5 nM] when
compared with mER (Kd = 0.2
nM). Antiestrogens, including
4-hydroxytamoxifen (OHT), ICI 182,780, and a novel compound, EM-800,
inhibit E2-dependent transactivation
efficiently. However, while OHT displays partial agonistic activity
with ER on a basal promoter linked to estrogen response elements in
Cos-1 cells, this effect is not observed with mERß. Cotransfection of
mERß and H-RasV12 causes enhanced activation
in the presence of E2. Mutagenesis of a serine
residue (position 60), located within a mitogen-activated protein
kinase consensus phosphorylation site abolishes the stimulatory effect
of Ras, suggesting that the activity of mERß is also regulated by the
mitogen-activated protein kinase pathway. Surprisingly, the coactivator
SRC-1 up-regulates mERß transactivation both in the absence and
presence of E2, and in vitro
interaction between SRC-1 and the ERß ligand-binding domain is
enhanced by E2. Moreover, the
ligand-independent stimulatory effect of SRC-1 on ERß transcriptional
activity is abolished by ICI 182,780, but not by OHT. Our results
demonstrate that while ERß shares many of the functional
characteristics of ER, the molecular mechanisms regulating the
transcriptional activity of mERß may be distinct from those of ER.
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U. Ohnemus, M. Uenalan, F. Conrad, B. Handjiski, L. Mecklenburg, M. Nakamura, J. Inzunza, J.-A. Gustafsson, and R. Paus Hair Cycle Control by Estrogens: Catagen Induction via Estrogen Receptor (ER)-{alpha} Is Checked by ER{beta} Signaling Endocrinology, March 1, 2005; 146(3): 1214 - 1225. [Abstract] [Full Text] [PDF]
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A. Bardin, F. Moll, R. Margueron, C. Delfour, M. L. Chu, T. Maudelonde, V. Cavailles, and P. Pujol Transcriptional and Posttranscriptional Regulation of Fibulin-1 by Estrogens Leads to Differential Induction of Messenger Ribonucleic Acid Variants in Ovarian and Breast Cancer Cells Endocrinology, February 1, 2005; 146(2): 760 - 768. [Abstract] [Full Text] [PDF]
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K. Stokes, B. Alston-Mills, and C. Teng Estrogen response element and the promoter context of the human and mouse lactoferrin genes influence estrogen receptor {alpha}-mediated transactivation activity in mammary gland cells J. Mol. Endocrinol., October 1, 2004; 33(2): 315 - 334. [Abstract] [Full Text] [PDF]
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A.G.B. Hurst, D.W. Goad, M. Mohan, and J.R. Malayer Independent Downstream Gene Expression Profiles in the Presence of Estrogen Receptor {alpha} or {beta} Biol Reprod, October 1, 2004; 71(4): 1252 - 1261. [Abstract] [Full Text] [PDF]
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 A Bardin, N Boulle, G Lazennec, F Vignon, and P Pujol Loss of ER{beta} expression as a common step in estrogen-dependent tumor progression Endocr. Relat. Cancer, September 1, 2004; 11(3): 537 - 551. [Abstract] [Full Text] [PDF]
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M. B. Hawkins and P. Thomas The Unusual Binding Properties of the Third Distinct Teleost Estrogen Receptor Subtype ER{beta}a Are Accompanied by Highly Conserved Amino Acid Changes in the Ligand Binding Domain Endocrinology, June 1, 2004; 145(6): 2968 - 2977. [Abstract] [Full Text] [PDF]
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J. Laganiere, G. B. Tremblay, C. R. Dufour, S. Giroux, F. Rousseau, and V. Giguere A Polymorphic Autoregulatory Hormone Response Element in the Human Estrogen-related Receptor {alpha} (ERR{alpha}) Promoter Dictates Peroxisome Proliferator-activated Receptor {gamma} Coactivator-1{alpha} Control of ERR{alpha} Expression J. Biol. Chem., April 30, 2004; 279(18): 18504 - 18510. [Abstract] [Full Text] [PDF]
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C. D. Toran-Allerand Minireview: A Plethora of Estrogen Receptors in the Brain: Where Will It End? Endocrinology, March 1, 2004; 145(3): 1069 - 1074. [Abstract] [Full Text] [PDF]
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B. Greco, L. S. Lubbers, and J. D. Blaustein Estrogen Receptor {beta} Messenger Ribonucleic Acid Expression in the Forebrain of Proestrous, Pregnant, and Lactating Female Rats Endocrinology, May 1, 2003; 144(5): 1869 - 1875. [Abstract] [Full Text] [PDF]
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Y. Bai and V. Giguere Isoform-Selective Interactions between Estrogen Receptors and Steroid Receptor Coactivators Promoted by Estradiol and ErbB-2 Signaling in Living Cells Mol. Endocrinol., April 1, 2003; 17(4): 589 - 599. [Abstract] [Full Text] [PDF]
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P. A. Orihuela, A. Parada-Bustamante, P. P. Cortes, C. Gatica, and H. B. Croxatto Estrogen Receptor, Cyclic Adenosine Monophosphate, and Protein Kinase A Are Involved in the Nongenomic Pathway by Which Estradiol Accelerates Oviductal Oocyte Transport in Cyclic Rats Biol Reprod, April 1, 2003; 68(4): 1225 - 1231. [Abstract] [Full Text] [PDF]
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 S. W. Cousins, M. E. Marin-Castano, D. G. Espinosa-Heidmann, A. Alexandridou, L. Striker, and S. Elliot Female Gender, Estrogen Loss, and Sub-RPE Deposit Formation in Aged Mice Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1221 - 1229. [Abstract] [Full Text] [PDF]
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Q. Lu, H. K. Surks, H. Ebling, W. E. Baur, D. Brown, D. C. Pallas, and R. H. Karas Regulation of Estrogen Receptor alpha -mediated Transcription by a Direct Interaction with Protein Phosphatase 2A J. Biol. Chem., February 7, 2003; 278(7): 4639 - 4645. [Abstract] [Full Text] [PDF]
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 M. Maira, C. Martens, E. Batsche, Y. Gauthier, and J. Drouin Dimer-Specific Potentiation of NGFI-B (Nur77) Transcriptional Activity by the Protein Kinase A Pathway and AF-1-Dependent Coactivator Recruitment Mol. Cell. Biol., February 1, 2003; 23(3): 763 - 776. [Abstract] [Full Text]
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M. E. Marin-Castano, S. J. Elliot, M. Potier, M. Karl, L. J. Striker, G. E. Striker, K. G. Csaky, and S. W. Cousins Regulation of Estrogen Receptors and MMP-2 Expression by Estrogens in Human Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 50 - 59. [Abstract] [Full Text] [PDF]
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D. A. Schreihofer, D. F. Rowe, E. F. Rissman, E. M. Scordalakes, J.-a. Gustafsson, and M. A. Shupnik Estrogen Receptor-{alpha} (ER{alpha}), But Not ER{beta}, Modulates Estrogen Stimulation of the ER{alpha}-Truncated Variant, TERP-1 Endocrinology, November 1, 2002; 143(11): 4196 - 4202. [Abstract] [Full Text] [PDF]
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N. Vasudevan, S. Ogawa, and D. Pfaff Estrogen and Thyroid Hormone Receptor Interactions: Physiological Flexibility by Molecular Specificity Physiol Rev, October 1, 2002; 82(4): 923 - 944. [Abstract] [Full Text] [PDF]
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H. T. Kim, B. C. Kim, I. Y. Kim, M. Mamura, D. H. Seong, J.-J. Jang, and S.-J. Kim Raloxifene, a Mixed Estrogen Agonist/Antagonist, Induces Apoptosis through Cleavage of BAD in TSU-PR1 Human Cancer Cells J. Biol. Chem., August 30, 2002; 277(36): 32510 - 32515. [Abstract] [Full Text] [PDF]
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P. Yi, S. Bhagat, R. Hilf, R. A. Bambara, and M. Muyan Differences in the Abilities of Estrogen Receptors to Integrate Activation Functions Are Critical for Subtype-Specific Transcriptional Responses Mol. Endocrinol., August 1, 2002; 16(8): 1810 - 1827. [Abstract] [Full Text] [PDF]
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N. Sharifi, A. E. Reuss, and S. Wray Prenatal LHRH Neurons in Nasal Explant Cultures Express Estrogen Receptor {beta} Transcript Endocrinology, July 1, 2002; 143(7): 2503 - 2507. [Abstract] [Full Text] [PDF]
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M. J. Evans, K. Lai, L. J. Shaw, D. C. Harnish, and C. C. Chadwick Estrogen Receptor {alpha} Inhibits IL-1{beta} Induction of Gene Expression in the Mouse Liver Endocrinology, July 1, 2002; 143(7): 2559 - 2570. [Abstract] [Full Text] [PDF]
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F. Gay, P. Barath, C. Desbois-Le Peron, R. Metivier, R. Le Guevel, D. Birse, and G. Salbert Multiple Phosphorylation Events Control Chicken Ovalbumin Upstream Promoter Transcription Factor I Orphan Nuclear Receptor Activity Mol. Endocrinol., June 1, 2002; 16(6): 1332 - 1351. [Abstract] [Full Text] [PDF]
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P. Yang, A. Kriatchko, and S. K. Roy Expression of ER-{alpha} and ER-{beta} in the Hamster Ovary: Differential Regulation by Gonadotropins and Ovarian Steroid Hormones Endocrinology, June 1, 2002; 143(6): 2385 - 2398. [Abstract] [Full Text] [PDF]
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A. Menuet, E. Pellegrini, I. Anglade, O. Blaise, V. Laudet, O. Kah, and F. Pakdel Molecular Characterization of Three Estrogen Receptor Forms in Zebrafish: Binding Characteristics, Transactivation Properties, and Tissue Distributions Biol Reprod, June 1, 2002; 66(6): 1881 - 1892. [Abstract] [Full Text] [PDF]
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J. M. Hall, D. P. McDonnell, and K. S. Korach Allosteric Regulation of Estrogen Receptor Structure, Function, and Coactivator Recruitment by Different Estrogen Response Elements Mol. Endocrinol., March 1, 2002; 16(3): 469 - 486. [Abstract] [Full Text] [PDF]
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S. Raghow, M. Z. Hooshdaran, S. Katiyar, and M. S. Steiner Toremifene Prevents Prostate Cancer in the Transgenic Adenocarcinoma of Mouse Prostate Model Cancer Res., March 1, 2002; 62(5): 1370 - 1376. [Abstract] [Full Text] [PDF]
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J. R. Schultz, M. A. Loven, V. M. S. Melvin, D. P. Edwards, and A. M. Nardulli Differential Modulation of DNA Conformation by Estrogen Receptors alpha and beta J. Biol. Chem., March 1, 2002; 277(10): 8702 - 8707. [Abstract] [Full Text] [PDF]
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A. A. Kowalski, L. G. Graddy, D. S. Vale-Cruz, I. Choi, B. S. Katzenellenbogen, F. A. Simmen, and R. C.M. Simmen Molecular Cloning of Porcine Estrogen Receptor-{beta} Complementary DNAs and Developmental Expression in Periimplantation Embryos Biol Reprod, March 1, 2002; 66(3): 760 - 769. [Abstract] [Full Text] [PDF]
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 C. A. Lamartiniere, J. Wang, M. Smith-Johnson, and I.-E. Eltoum Daidzein: Bioavailability, Potential for Reproductive Toxicity, and Breast Cancer Chemoprevention in Female Rats Toxicol. Sci., February 1, 2002; 65(2): 228 - 238. [Abstract] [Full Text] [PDF]
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P. H. Driggers, J. H. Segars, and D. M. Rubino The Proto-oncoprotein Brx Activates Estrogen Receptor beta by a p38 Mitogen-activated Protein Kinase Pathway J. Biol. Chem., December 7, 2001; 276(50): 46792 - 46797. [Abstract] [Full Text] [PDF]
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 B. S. McEwen Genome and Hormones: Gender Differences in Physiology: Invited Review: Estrogens effects on the brain: multiple sites and molecular mechanisms J Appl Physiol, December 1, 2001; 91(6): 2785 - 2801. [Abstract] [Full Text] [PDF]
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B. Greco, E. A. Allegretto, M. J. Tetel, and J. D. Blaustein Coexpression of ER{beta} with ER{alpha} and Progestin Receptor Proteins in the Female Rat Forebrain: Effects of Estradiol Treatment Endocrinology, December 1, 2001; 142(12): 5172 - 5181. [Abstract] [Full Text] [PDF]
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A. Warnmark, A. Wikstrom, A. P. H. Wright, J.-A. Gustafsson, and T. Hard The N-terminal Regions of Estrogen Receptor alpha and beta Are Unstructured in Vitro and Show Different TBP Binding Properties J. Biol. Chem., November 30, 2001; 276(49): 45939 - 45944. [Abstract] [Full Text] [PDF]
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E. R. Levin Genome and Hormones: Gender Differences in Physiology: Invited Review: Cell localization, physiology, and nongenomic actions of estrogen receptors J Appl Physiol, October 1, 2001; 91(4): 1860 - 1867. [Abstract] [Full Text] [PDF]
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R. H. Karas, H. Schulten, G. Pare, M. J. Aronovitz, C. Ohlsson, J.-A. Gustafsson, and M. E. Mendelsohn Effects of Estrogen on the Vascular Injury Response in Estrogen Receptor {alpha},{beta} (Double) Knockout Mice Circ. Res., September 14, 2001; 89(6): 534 - 539. [Abstract] [Full Text] [PDF]
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 P. Devanesan, R. J. Santen, W. P. Bocchinfuso, K. S. Korach, E. G. Rogan, and E. Cavalieri Catechol estrogen metabolites and conjugates in mammary tumors and hyperplastic tissue from estrogen receptor-{alpha} knock-out (ERKO)/Wnt-1 mice: implications for initiation of mammary tumors Carcinogenesis, September 1, 2001; 22(9): 1573 - 1576. [Abstract] [Full Text] [PDF]
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D. Lu, Y. Kiriyama, K. Y. Lee, and V. Giguere Transcriptional Regulation of the Estrogen-inducible pS2 Breast Cancer Marker Gene by the ERR Family of Orphan Nuclear Receptors Cancer Res., September 1, 2001; 61(18): 6755 - 6761. [Abstract] [Full Text] [PDF]
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D. A. Schreihofer, E. M. Resnick, V. Y. Lin, and M. A. Shupnik Ligand-Independent Activation of Pituitary ER: Dependence on PKA-Stimulated Pathways Endocrinology, August 1, 2001; 142(8): 3361 - 3368. [Abstract] [Full Text] [PDF]
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C. M. Klinge Estrogen receptor interaction with estrogen response elements Nucleic Acids Res., July 15, 2001; 29(14): 2905 - 2919. [Abstract] [Full Text] [PDF]
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 I. Leav, K.-M. Lau, J. Y. Adams, J. E. McNeal, M.-E. Taplin, J. Wang, H. Singh, and S.-M. Ho Comparative Studies of the Estrogen Receptors {beta} and {{alpha}} and the Androgen Receptor in Normal Human Prostate Glands, Dysplasia, and in Primary and Metastatic Carcinoma Am. J. Pathol., July 1, 2001; 159(1): 79 - 92. [Abstract] [Full Text] [PDF]
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H. Cardenas, K.A. Burke, R.M. Bigsby, W.F. Pope, and K.P. Nephew Estrogen Receptor {beta} in the Sheep Ovary During the Estrous Cycle and Early Pregnancy Biol Reprod, July 1, 2001; 65(1): 128 - 134. [Abstract] [Full Text] [PDF]
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L. O'Donnell, K. M. Robertson, M. E. Jones, and E. R. Simpson Estrogen and Spermatogenesis Endocr. Rev., June 1, 2001; 22(3): 289 - 318. [Abstract] [Full Text] [PDF]
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S. F. Palter, A. B. Tavares, A. Hourvitz, J. D. Veldhuis, and E. Y. Adashi Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis? Endocr. Rev., June 1, 2001; 22(3): 389 - 424. [Abstract] [Full Text] [PDF]
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K. S. Bramlett, Y. Wu, and T. P. Burris Ligands Specify Coactivator Nuclear Receptor (NR) Box Affinity for Estrogen Receptor Subtypes Mol. Endocrinol., June 1, 2001; 15(6): 909 - 922. [Abstract] [Full Text] [PDF]
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C. Guo, L. Savage, K. D. Sarge, and O.-K. Park-Sarge Gonadotropins Decrease Estrogen Receptor-{beta} Messenger Ribonucleic Acid Stability in Rat Granulosa Cells Endocrinology, June 1, 2001; 142(6): 2230 - 2237. [Abstract] [Full Text] [PDF]
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 G. V. Childs, G. Unabia, and S. Komak Differential Expression of Estradiol Receptors Alpha and Beta by Gonadotropes During the Estrous Cycle J. Histochem. Cytochem., May 1, 2001; 49(5): 665 - 666. [Abstract] [Full Text]
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J. Takeyama, T. Suzuki, S. Inoue, C. Kaneko, H. Nagura, N. Harada, and H. Sasano Expression and Cellular Localization of Estrogen Receptors {{alpha}} and {beta} in the Human Fetus J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2258 - 2262. [Abstract] [Full Text]
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G. B. Tremblay, T. Kunath, D. Bergeron, L. Lapointe, C. Champigny, J.-A. Bader, J. Rossant, and V. Giguère Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR{beta} Genes & Dev., April 1, 2001; 15(7): 833 - 838. [Abstract] [Full Text]
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H. O. D. Critchley, R. M. Brenner, T. A. Henderson, K. Williams, N. R. Nayak, O. D. Slayden, M. R. Millar, and P. T. K. Saunders Estrogen Receptor {beta}, But Not Estrogen Receptor {{alpha}}, Is Present in the Vascular Endothelium of the Human and Nonhuman Primate Endometrium J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1370 - 1378. [Abstract] [Full Text]
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G. LECCE, G. MEDURI, M. ANCELIN, C. BERGERON, and M. PERROT-APPLANAT Presence of Estrogen Receptor {beta} in the Human Endometrium through the Cycle: Expression in Glandular, Stromal, and Vascular Cells J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1379 - 1386. [Abstract] [Full Text]
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M. J. Weyant, A. M. Carothers, N. N. Mahmoud, H. L. Bradlow, H. Remotti, R. T. Bilinski, and M. M. Bertagnolli Reciprocal Expression of ER{{alpha}} and ER{beta} Is Associated with Estrogen-mediated Modulation of Intestinal Tumorigenesis Cancer Res., March 1, 2001; 61(6): 2547 - 2551. [Abstract] [Full Text]
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R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance Pharmacol. Rev., March 1, 2001; 53(1): 25 - 72. [Abstract] [Full Text] [PDF]
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