![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 3, 1262-1272, March 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
and 
* Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, California 94143-0556;
Department of Cellular and Molecular Pharmacology, Center for Reproductive Sciences, University of California San Francisco, San Francisco, California 94143-0556; and
GeneTex, Inc., San Antonio, Texas 78245
Submitted June 4, 2003;
Revised November 7, 2003;
Accepted November 19, 2003
Monitoring Editor: Marvin P. Wickens
Estrogens and selective estrogen receptor modulators (SERMs) interact with estrogen receptor (ER) 
and 
to activate or repress gene transcription. To understand how estrogens and SERMs exert tissue-specific effects, we performed microarray analysis to determine whether ER or ER regulate different target genes in response to estrogens and SERMs. We prepared human U2OS osteosarcoma cells that are stably transfected with a tetracycline-inducible vector to express ER or ER. Western blotting, immunohistochemistry, and immunoprecipitation studies confirmed that U2OS-ER cells synthesized only ER and that U2OS-ER cells expressed exclusively ER. U2OS-ER and U2OS-ER cells were treated either with 17-estradiol (E2), raloxifene, and tamoxifen for 18 h. Labeled cRNAs were hybridized with U95Av2 GeneChips (Affymetrix). A total of 228, 190, and 236 genes were significantly activated or repressed at least 1.74-fold in U2OS-ER and U2OS-ER cells by E2, raloxifene, and tamoxifen, respectively. Most genes regulated in ER cells in response to E2, raloxifene, and tamoxifen were distinct from those regulated in ER cells. Only 38 of the 228 (17%) genes were regulated by E2 in both U2OS-ER and U2OS-ER cells. Raloxifene and tamoxifen regulated only 27% of the same genes in both the ER and ER cells. A subset of genes involved in bone-related activities regulated by E2, raloxifene, and tamoxifen were also distinct. Our results demonstrate that most genes regulated by ER are distinct from those regulated by ER in response to E2 and SERMs. These results indicate that estrogens and SERMs exert tissue-specific effects by regulating unique sets of targets genes through ER and ER
Abbreviations used: ChIP, chromatin immunoprecipitation; E2, 17-estradiol; ER, estrogen receptor(s); ERE, estrogen response element; K19, keratin 19; PBS, phosphate-buffered saline; RT, reverse transcription; SERM, selective estrogen receptor modulator(s); WISP-2, WNT1-inducible signaling pathway protein-2.
Online version of this article contains supplementary material. Online version is available at www.molbiolcell.org.
Corresponding author. E-mail address: leitmand{at}obgyn.ucsf.edu.
This article has been cited by other articles:
|
|
 |
|
  D. J Kojetin, T. P Burris, E. V Jensen, and S. A Khan Implications of the binding of tamoxifen to the coactivator recognition site of the estrogen receptor Endocr. Relat. Cancer, December 1, 2008; 15(4): 851 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kharode, P. V. N. Bodine, C. P. Miller, C. R. Lyttle, and B. S. Komm The Pairing of a Selective Estrogen Receptor Modulator, Bazedoxifene, with Conjugated Estrogens as a New Paradigm for the Treatment of Menopausal Symptoms and Osteoporosis Prevention Endocrinology, December 1, 2008; 149(12): 6084 - 6091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Yarrow, C. F. Conover, A. V. Purandare, A. M. Bhakta, N. Zheng, B. Conrad, M. K. Altman, S. E. Franz, T. J. Wronski, and S. E. Borst Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1213 - E1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Gonzales, M. J. Tetel, and C. K. Wagner Estrogen Receptor (ER) {beta} Modulates ER{alpha} Responses to Estrogens in the Developing Rat Ventromedial Nucleus of the Hypothalamus Endocrinology, September 1, 2008; 149(9): 4615 - 4621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Hawse, M. Subramaniam, D. G. Monroe, A. H. Hemmingsen, J. N. Ingle, S. Khosla, M. J. Oursler, and T. C. Spelsberg Estrogen Receptor {beta} Isoform-Specific Induction of Transforming Growth Factor {beta}-Inducible Early Gene-1 in Human Osteoblast Cells: An Essential Role for the Activation Function 1 Domain Mol. Endocrinol., July 1, 2008; 22(7): 1579 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, S. L Nott, Y. Huang, R. Hilf, R. A Bambara, X. Qiu, A. Yakovlev, S. Welle, and M. Muyan Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17{beta}-estradiol-estrogen receptor {beta} is uncoupled from the induction of phenotypic changes in cell models J. Mol. Endocrinol., May 1, 2008; 40(5): 211 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Chang, T. H. Charn, S.-H. Park, W. G. Helferich, B. Komm, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen Receptors {alpha} and {beta} as Determinants of Gene Expression: Influence of Ligand, Dose, and Chromatin Binding Mol. Endocrinol., May 1, 2008; 22(5): 1032 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Denger, T. Bahr-Ivacevic, H. Brand, G. Reid, J. Blake, M. Seifert, C.-Y. Lin, K. May, V. Benes, E. T. Liu, et al. Transcriptome Profiling of Estrogen-Regulated Genes in Human Primary Osteoblasts Reveals an Osteoblast-Specific Regulation of the Insulin-Like Growth Factor Binding Protein 4 Gene Mol. Endocrinol., February 1, 2008; 22(2): 361 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Levy, D. Tatomer, C. B. Herber, X. Zhao, H. Tang, T. Sargeant, L. J. Ball, J. Summers, T. P. Speed, and D. C. Leitman Differential Regulation of Native Estrogen Receptor-Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene Mol. Endocrinol., February 1, 2008; 22(2): 287 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Hardman, E. Emmerson, L. Campbell, and G. S. Ashcroft Selective Estrogen Receptor Modulators Accelerate Cutaneous Wound Healing in Ovariectomized Female Mice Endocrinology, February 1, 2008; 149(2): 551 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cvoro, D. Tatomer, M.-K. Tee, T. Zogovic, H. A. Harris, and D. C. Leitman Selective Estrogen Receptor- Agonists Repress Transcription of Proinflammatory Genes J. Immunol., January 1, 2008; 180(1): 630 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bai, S. M. Houten, A. Huber, V. Schreiber, M. Watanabe, B. Kiss, G. de Murcia, J. Auwerx, and J. M.-d. Murcia Peroxisome Proliferator-activated Receptor (PPAR)-2 Controls Adipocyte Differentiation and Adipose Tissue Function through the Regulation of the Activity of the Retinoid X Receptor/PPAR{gamma} Heterodimer J. Biol. Chem., December 28, 2007; 282(52): 37738 - 37746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stygar, B. Masironi, H. Eriksson, and L. Sahlin Studies on estrogen receptor (ER) {alpha} and {beta} responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists J. Endocrinol., July 1, 2007; 194(1): 101 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Schultz-Norton, K. A. Walt, Y. S. Ziegler, I. X. McLeod, J. R. Yates, L. T. Raetzman, and A. M. Nardulli The Deoxyribonucleic Acid Repair Protein Flap Endonuclease-1 Modulates Estrogen-Responsive Gene Expression Mol. Endocrinol., July 1, 2007; 21(7): 1569 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Levy, X. Zhao, H. Tang, R. B. Jaffe, T. P. Speed, and D. C. Leitman Multiple Transcription Factor Elements Collaborate with Estrogen Receptor {alpha} to Activate an Inducible Estrogen Response Element in the NKG2E Gene Endocrinology, July 1, 2007; 148(7): 3449 - 3458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M Johnson, M. Maleki-Dizaji, J. A Styles, and I. N H White Ishikawa cells exhibit differential gene expression profiles in response to oestradiol or 4-hydroxytamoxifen Endocr. Relat. Cancer, June 1, 2007; 14(2): 337 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-C. Leung, J. Brce, N. Doyle, H. J. Lee, G. M. Leong, K. Sjogren, and K. K. Y. Ho Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases Endocrinology, May 1, 2007; 148(5): 2417 - 2423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cvoro, S. Paruthiyil, J. O. Jones, C. Tzagarakis-Foster, N. J. Clegg, D. Tatomer, R. T. Medina, M. Tagliaferri, F. Schaufele, T. S. Scanlan, et al. Selective Activation of Estrogen Receptor-{beta} Transcriptional Pathways by an Herbal Extract Endocrinology, February 1, 2007; 148(2): 538 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Li, M. J. Meyer, Curtis. P. Van Tassell, T. S. Sonstegard, E. E. Connor, M. E. Van Amburgh, Y. R. Boisclair, and A. V. Capuco Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis Physiol Genomics, January 12, 2007; 27(1): 42 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Monroe, F. J. Secreto, J. R. Hawse, M. Subramaniam, S. Khosla, and T. C. Spelsberg Estrogen Receptor Isoform-specific Regulation of the Retinoblastoma-binding Protein 1 (RBBP1) Gene: ROLES OF AF1 AND ENHANCER ELEMENTS J. Biol. Chem., September 29, 2006; 281(39): 28596 - 28604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Frasor, E. C. Chang, B. Komm, C.-Y. Lin, V. B. Vega, E. T. Liu, L. D. Miller, J. Smeds, J. Bergh, and B. S. Katzenellenbogen Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res., July 15, 2006; 66(14): 7334 - 7340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Hsieh, S. S. Rajan, S. K. Sharma, Y. Guo, E. R. DeSombre, M. Mrksich, and G. L. Greene Identification of Ligands with Bicyclic Scaffolds Provides Insights into Mechanisms of Estrogen Receptor Subtype Selectivity J. Biol. Chem., June 30, 2006; 281(26): 17909 - 17919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Dubal, S. W. Rau, P. J. Shughrue, H. Zhu, J. Yu, A. B. Cashion, S. Suzuki, L. M. Gerhold, M. B. Bottner, S. B. Dubal, et al. Differential Modulation of Estrogen Receptors (ERs) in Ischemic Brain Injury: A Role for ER{alpha} in Estradiol-Mediated Protection against Delayed Cell Death Endocrinology, June 1, 2006; 147(6): 3076 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Wang, N. Shah, C. Pantoja, S. H. Meijsing, J. D. Ho, T. S. Scanlan, and K. R. Yamamoto Novel arylpyrazole compounds selectively modulate glucocorticoid receptor regulatory activity. Genes & Dev., March 15, 2006; 20(6): 689 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S C J P Gielen, L C M Kuhne, P C Ewing, L J Blok, and C W Burger Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study Endocr. Relat. Cancer, December 1, 2005; 12(4): 1037 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V X Jin, H Sun, T T Pohar, S Liyanarachchi, S K Palaniswamy, T H-M Huang, and R V Davuluri ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes J. Mol. Endocrinol., October 1, 2005; 35(2): 225 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C.J.P. Gielen, C. W. Burger, L. C.M. Kuhne, P. Hanifi-Moghaddam, and L. J. Blok Analysis off Estrogen Agonism and Antagonism of Tamoxifen, Raloxifene, and ICI182780 in Endometrial Cancer Cells: A Putative Role for the Epidermal Growth Factor Receptor Ligand Amphiregulin Reproductive Sciences, October 1, 2005; 12(7): e55 - e66. [Abstract] [PDF]
|
|
|
|
|
|
D. G. Monroe, F. J. Secreto, M. Subramaniam, B. J. Getz, S. Khosla, and T. C. Spelsberg Estrogen Receptor {alpha} and {beta} Heterodimers Exert Unique Effects on Estrogen- and Tamoxifen-Dependent Gene Expression in Human U2OS Osteosarcoma Cells Mol. Endocrinol., June 1, 2005; 19(6): 1555 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Cheung, M. L. Acevedo, P. A. Cole, and W. L. Kraus Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1 PNAS, January 18, 2005; 102(3): 559 - 564. [Abstract] [Full Text] [PDF]
|
|
