This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kennedy, A. M. Articles by Maran, A. Search for Related Content PubMed PubMed Citation Articles by Kennedy, A. M. Articles by Maran, A.

17ß-Estradiol-Dependent Activation of Signal Transducer and Activator of Transcription-1 in Human Fetal Osteoblasts Is Dependent on Src Kinase Activity

Departments of Orthopedics (A.M.K., K.L.S., M.Z., R.T.T., A.M.) and Biochemistry and Molecular Biology (R.T.T., T.C.S.), Mayo Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Dr. A. Maran, 3-69 Medical Sciences Building, Department of Orthopedics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905. E-mail: maran{at}mayo.edu.

Estrogen is essential for normal growth and remodeling of bone. Although the mechanism of estrogen action on bone cells has been widely investigated, the full spectrum of signal transduction pathways activated by estrogen is unknown. In this report, we investigate the effects of the gonadal hormone 17ß-estradiol on the regulation of signal transducer and activator of transcription-1 (Stat1) protein in cultured human fetal osteoblast cells, devoid of the classical estrogen receptors (ERs). 17ß-Estradiol (10 nM) led to rapid (within 15 min) activation of Stat1 protein as indicated by increases in tyrosine phosphorylation and DNA binding activity. Also, 17ß-estradiol increased -activated sequence-dependent transcription in transient transfection assays, suggesting an increase in Stat protein-dependent transcription. Estrogen-dependent Stat1 activation was blocked in cells that transiently express dominant-negative Stat1 mutant protein. Activation of Stat1 by 17ß-estradiol was not inhibited by ER antagonist ICI 182,780, providing further evidence that it is not dependent on classical ERs. 17ß-Estradiol induced rapid (within 15 min) Stat1 phosphorylation and stimulated activated sequence-dependent transcription in ER-negative breast cancer cells, indicating that these results are not unique to bone cells. The rapid estrogenic effect involving the phosphorylation and activation of Stat1 was blocked in the presence of Src family kinase inhibitor PP2; activated Stat1 was associated with Src protein in estrogen-treated cells. These findings indicate the requirement for Src kinase pathways in estrogen-mediated Stat1 activation. Thus, the ER-independent activation of Stat1 in 17ß-estradiol-treated osteoblast and breast cancer cells may partially mediate the actions of estrogen on target cells.

This article has been cited by other articles:

				K. Vagnerova, I. P. Koerner, and P. D. Hurn Gender and the Injured Brain Anesth. Analg., July 1, 2008; 107(1): 201 - 214. [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]

				M. M. Joyce, R. C. Burghardt, R. D. Geisert, J. R. Burghardt, R. N. Hooper, J. W. Ross, M. D. Ashworth, and G. A. Johnson Pig Conceptuses Secrete Estrogen and Interferons to Differentially Regulate Uterine STAT1 in a Temporal and Cell Type-Specific Manner Endocrinology, September 1, 2007; 148(9): 4420 - 4431. [Abstract] [Full Text] [PDF]

				J. Rajasingh, E. Bord, G. Qin, M. Ii, M. Silver, H. Hamada, D. Ahluwalia, D. Goukassian, Y. Zhu, D. W. Losordo, et al. Enhanced Voluntary Alcohol Consumption after Estrogen Supplementation Negates Estrogen-Mediated Vascular Repair in Ovariectomized Mice Endocrinology, August 1, 2007; 148(8): 3618 - 3624. [Abstract] [Full Text] [PDF]

				P. I. Moreira, J. Custodio, A. Moreno, C. R. Oliveira, and M. S. Santos Tamoxifen and Estradiol Interact with the Flavin Mononucleotide Site of Complex I Leading to Mitochondrial Failure J. Biol. Chem., April 14, 2006; 281(15): 10143 - 10152. [Abstract] [Full Text] [PDF]

				K. Kawana, Y. Kawana, and D. J. Schust Female Steroid Hormones Use Signal Transducers and Activators of Transcription Protein-Mediated Pathways to Modulate the Expression of T-bet in Epithelial Cells: A Mechanism for Local Immune Regulation in the Human Reproductive Tract Mol. Endocrinol., August 1, 2005; 19(8): 2047 - 2059. [Abstract] [Full Text] [PDF]