| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Receptor Biology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Address all correspondence and requests for reprints to: Kenneth S. Korach, Receptor Biology Section, National Institute of Environmental Health Sciences, P.O. Box 12233, MD B3-02, Research Triangle Park, North Carolina 27709. E-mail: korach{at}niehs.nih.gov.
Recent clinical studies estimate that 60–70% of human ovarian and breast cancers overexpress the estrogen receptor (ER). However, despite the established mitogenic effects of estrogen in these tumors, proliferative markers of hormone action are limited. In the current study, we report that the growth stimulatory cytokine stromal cell-derived factor 1 (SDF-1) is a bona fide target of estrogen action in ER
-positive human ovarian and breast cancer cells. Notably, estradiol treatment of BG-1 (ovarian carcinoma) and MCF-7 (breast carcinoma) cells leads to rapid and robust induction of the SDF-1 and ß isoforms. This response is blocked by the pure ER antagonist ICI 182,780 and is not apparent in ER-negative ovarian cells, indicating that SDF-1 regulation is ER mediated. Treatment with the protein synthesis inhibitor cycloheximide had no effect on estradiol induction of induction of SDF-1 mRNA levels mRNA levels, demonstrating that SDF-1 is a direct target of ER. SDF-1 protein levels, although undetectable under basal conditions, were strikingly increased by hormone both intracellularly and in the media of cultured BG-1 and MCF-7 cells. In cell proliferation assays, the mitogenic effects of estradiol were neutralized by addition of an SDF-1 antibody and mimicked by the addition of exogenous SDF-1 protein, indicating that SDF-1 mediates the proliferative actions of hormone. Furthermore, activation of the SDF-1 receptor CXCR4 stimulated BG-1 and MCF-7 cell proliferation in a manner comparable to estradiol. Taken together, these results demonstrate a novel estrogen-mediated paracrine pathway for inducing cancer cell proliferation and suggest that SDF-1 and CXCR4 may represent novel therapeutic targets in ER-positive ovarian and breast tumors.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  S. M. Boue, S. L. Tilghman, S. Elliott, M. C. Zimmerman, K. Y. Williams, F. Payton-Stewart, A. P. Miraflor, M. H. Howell, B. Y. Shih, C. H. Carter-Wientjes, et al. Identification of the Potent Phytoestrogen Glycinol in Elicited Soybean (Glycine max) Endocrinology, May 1, 2009; 150(5): 2446 - 2453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lee, J. M. Kim, and E. J. Lee Functional expression of CXCR4 in somatotrophs: CXCL12 activates GH gene, GH production and secretion, and cellular proliferation J. Endocrinol., November 1, 2008; 199(2): 191 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Stein, C.-y. Chang, D. A. Kazmin, J. Way, T. Schroeder, M. Wergin, M. W. Dewhirst, and D. P. McDonnell Estrogen-Related Receptor {alpha} Is Critical for the Growth of Estrogen Receptor-Negative Breast Cancer Cancer Res., November 1, 2008; 68(21): 8805 - 8812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qu, S. Van Ginkel, A. M. Roy, L. Westbrook, M. Nasrin, Y. Maxuitenko, A. R. Frost, D. Carey, W. Wang, R. Li, et al. Vascular Endothelial Growth Factor Reduces Tamoxifen Efficacy and Promotes Metastatic Colonization and Desmoplasia in Breast Tumors Cancer Res., August 1, 2008; 68(15): 6232 - 6240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. U. Woo, J. W. Bae, C. H. Kim, J. B. Lee, and B. W. Koo A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer Ann. Surg. Oncol., January 1, 2008; 15(1): 281 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pattarozzi, M. Gatti, F. Barbieri, R. Wurth, C. Porcile, G. Lunardi, A. Ratto, R. Favoni, A. Bajetto, A. Ferrari, et al. 17 -Estradiol Promotes Breast Cancer Cell Proliferation-Inducing Stromal Cell-Derived Factor-1-Mediated Epidermal Growth Factor Receptor Transactivation: Reversal by Gefitinib Pretreatment Mol. Pharmacol., January 1, 2008; 73(1): 191 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Kleinman, M. R. Greives, S. S. Churgin, K. M. Blechman, E. I. Chang, D. J. Ceradini, O. M. Tepper, and G. C. Gurtner Hypoxia-Induced Mediators of Stem/Progenitor Cell Trafficking Are Increased in Children With Hemangioma Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2664 - 2670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Hsu, D. Yoon, H. H. Choi, F. Wang, R. T. Taylor, N. Chen, R. Zhang, and O. Hankinson A Proposed Mechanism for the Protective Effect of Dioxin against Breast Cancer Toxicol. Sci., August 1, 2007; 98(2): 436 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Eeckhoute, E. K. Keeton, M. Lupien, S. A. Krum, J. S. Carroll, and M. Brown Positive Cross-Regulatory Loop Ties GATA-3 to Estrogen Receptor {alpha} Expression in Breast Cancer Cancer Res., July 1, 2007; 67(13): 6477 - 6483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, D. Medina, A. Tsimelzon, S. K. Mohsin, S. Mao, Y. Wu, and D. C. Allred Alterations of Gene Expression in the Development of Early Hyperplastic Precursors of Breast Cancer Am. J. Pathol., July 1, 2007; 171(1): 252 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lengi, R. A. Phillips, E. Karpuzoglu, and S. A. Ahmed Estrogen selectively regulates chemokines in murine splenocytes J. Leukoc. Biol., April 1, 2007; 81(4): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Harvey, P. Mellor, H. Eldaly, T. W.J. Lennard, J. A. Kirby, and S. Ali Inhibition of CXCR4-Mediated Breast Cancer Metastasis: A Potential Role for Heparinoids? Clin. Cancer Res., March 1, 2007; 13(5): 1562 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kryczek, S. Wei, E. Keller, R. Liu, and W. Zou Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis Am J Physiol Cell Physiol, March 1, 2007; 292(3): C987 - C995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Albanito, A. Madeo, R. Lappano, A. Vivacqua, V. Rago, A. Carpino, T. I. Oprea, E. R. Prossnitz, A. M. Musti, S. Ando, et al. G Protein-Coupled Receptor 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17{beta}-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells Cancer Res., February 15, 2007; 67(4): 1859 - 1866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sutton, V. Friand, S. Brule-Donneger, T. Chaigneau, M. Ziol, O. Sainte-Catherine, A. Poire, L. Saffar, M. Kraemer, J. Vassy, et al. Stromal Cell-Derived Factor-1/Chemokine (C-X-C Motif) Ligand 12 Stimulates Human Hepatoma Cell Growth, Migration, and Invasion Mol. Cancer Res., January 1, 2007; 5(1): 21 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Meijer, I. S. Zeelenberg, B. Sipos, and E. Roos The CXCR5 Chemokine Receptor Is Expressed by Carcinoma Cells and Promotes Growth of Colon Carcinoma in the Liver Cancer Res., October 1, 2006; 66(19): 9576 - 9582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Chang, J. Frasor, B. Komm, and B. S. Katzenellenbogen Impact of Estrogen Receptor {beta} on Gene Networks Regulated by Estrogen Receptor {alpha} in Breast Cancer Cells Endocrinology, October 1, 2006; 147(10): 4831 - 4842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Wood, S. E. Appt, T. B. Clarkson, A. A. Franke, C. J. Lees, D. R. Doerge, and J. M. Cline Effects of High-Dose Soy Isoflavones and Equol on Reproductive Tissues in Female Cynomolgus Monkeys Biol Reprod, September 1, 2006; 75(3): 477 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhu, L. L. Sullivan, S. S. Nair, C. C. Williams, A. K. Pandey, L. Marrero, R. K. Vadlamudi, and F. E. Jones Coregulation of Estrogen Receptor by ERBB4/HER4 Establishes a Growth-Promoting Autocrine Signal in Breast Tumor Cells Cancer Res., August 15, 2006; 66(16): 7991 - 7998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ueda, N. F. Neel, E. Schutyser, D. Raman, and A. Richmond Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells Cancer Res., June 1, 2006; 66(11): 5665 - 5675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Florio, S. Casagrande, F. Diana, A. Bajetto, C. Porcile, G. Zona, S. Thellung, S. Arena, A. Pattarozzi, A. Corsaro, et al. Chemokine Stromal Cell-Derived Factor 1{alpha} Induces Proliferation and Growth Hormone Release in GH4C1 Rat Pituitary Adenoma Cell Line through Multiple Intracellular Signals Mol. Pharmacol., February 1, 2006; 69(2): 539 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kishimoto, Z. Wang, P. Bhat-Nakshatri, D. Chang, R. Clarke, and H. Nakshatri The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1{alpha}/CXCL12 Carcinogenesis, October 1, 2005; 26(10): 1706 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1-CXCR4 Axis Stem Cells, August 1, 2005; 23(7): 879 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Keeton and M. Brown Cell Cycle Progression Stimulated by Tamoxifen-Bound Estrogen Receptor-{alpha} and Promoter-Specific Effects in Breast Cancer Cells Deficient in N-CoR and SMRT Mol. Endocrinol., June 1, 2005; 19(6): 1543 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Laverdiere, B. H. Hoang, R. Yang, R. Sowers, J. Qin, P. A. Meyers, A. G. Huvos, J. H. Healey, and R. Gorlick Messenger RNA Expression Levels of CXCR4 Correlate with Metastatic Behavior and Outcome in Patients with Osteosarcoma Clin. Cancer Res., April 1, 2005; 11(7): 2561 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Jones, N. J. Hannan, T. J. Kaitu'u, J. Zhang, and L. A. Salamonsen Identification of Chemokines Important for Leukocyte Recruitment to the Human Endometrium at the Times of Embryo Implantation and Menstruation J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6155 - 6167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. P. Smith, K. E. Luker, J. R. Garbow, J. L. Prior, E. Jackson, D. Piwnica-Worms, and G. D. Luker CXCR4 Regulates Growth of Both Primary and Metastatic Breast Cancer Cancer Res., December 1, 2004; 64(23): 8604 - 8612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Gaben, C. Saucier, M. Bedin, G. Redeuilh, and J. Mester Mitogenic Activity of Estrogens in Human Breast Cancer Cells Does Not Rely on Direct Induction of Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase or Phosphatidylinositol 3-Kinase Mol. Endocrinol., November 1, 2004; 18(11): 2700 - 2713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wu, D.-J. Li, M.-M. Yuan, Y. Zhu, and M.-Y. Wang The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells Biol Reprod, June 1, 2004; 70(6): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frasor, F. Stossi, J. M. Danes, B. Komm, C. R. Lyttle, and B. S. Katzenellenbogen Selective Estrogen Receptor Modulators: Discrimination of Agonistic versus Antagonistic Activities by Gene Expression Profiling in Breast Cancer Cells Cancer Res., February 15, 2004; 64(4): 1522 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Coser, J. Chesnes, J. Hur, S. Ray, K. J. Isselbacher, and T. Shioda Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray PNAS, November 25, 2003; 100(24): 13994 - 13999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frasor, J. M. Danes, B. Komm, K. C. N. Chang, C. R. Lyttle, and B. S. Katzenellenbogen Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype Endocrinology, October 1, 2003; 144(10): 4562 - 4574. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
