Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000018947.95555.65
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:2653.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Steroid Receptor Coactivator-3 Is Required for Inhibition of Neointima Formation by Estrogen
From the Departments of Molecular and Cellular Biology (Y.Y, L.L, J.X.) and Medicine (D.A.T.), Baylor College of Medicine, Houston, Tex.
Correspondence to Jianming Xu, PhD, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail jxu{at}bcm.tmc.edu
Background— The vasoprotective effects of estrogen are mediated by estrogen receptors (ERs). ERs are transcription factors that require coactivators to exert transcriptional activity. The steroid receptor coactivator-3 (SRC-3, also known as pCIP, AIB1, ACTR, and TRAM-1) interacts with estrogen-bound ERs and strongly coactivates the transcription of target genes in cultured cells. This study has characterized the expression of SRC-3 in cardiovascular tissue and the role of SRC-3 in estrogen-dependent vasoprotection from vascular injury.
Methods and Results— Phenotypically normal SRC-3+/- mice with a knock-in LacZ reporter were used to characterize SRC-3 expression by X-gal staining within the cardiovascular system. Staining signals were specifically detected in vascular smooth muscle cells and endothelial cells but not in myocardial cells. The role of SRC-3 during vascular remodeling was analyzed using a unilateral carotid ligation model. The extent of neointima formation in SRC-3-/- mice was significantly higher than in wild-type mice, and this difference was diminished after depletion of estrogen by ovariectomy. After ovariectomy, neointimal growth in wild-type mice was almost completely inhibited by estrogen treatment but only partially inhibited in SRC-3-/- mice. Furthermore, estrogen treatment resulted in reduced inhibition of intimal cell proliferation in SRC-3-/- mice.
Conclusions— SRC-3 is highly expressed in vascular smooth muscle cells and endothelial cells. The loss of SRC-3 function causes a decrease in sensitivity of estrogen-mediated inhibition of neointimal growth, which may be attributable to an insufficient suppression of vascular cell proliferation. These results indicate that SRC-3 largely facilitates ER-dependent vasoprotective effects under conditions of vascular trauma.
Key Words: hormones • receptors • arteries
This article has been cited by other articles:
 |
|
 |
|
  L. Liao, X. Chen, S. Wang, A. F. Parlow, and J. Xu Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression Mol. Cell. Biol., April 1, 2008; 28(7): 2460 - 2469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kawagoe, M. Ohmichi, S. Tsutsumi, T. Ohta, K. Takahashi, and H. Kurachi Mechanism of the Divergent Effects of Estrogen on the Cell Proliferation of Human Umbilical Endothelial Versus Aortic Smooth Muscle Cells Endocrinology, December 1, 2007; 148(12): 6092 - 6099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Amazit, L. Pasini, A. T. Szafran, V. Berno, R.-C. Wu, M. Mielke, E. D. Jones, M. G. Mancini, C. A. Hinojos, B. W. O'Malley, et al. Regulation of SRC-3 Intercompartmental Dynamics by Estrogen Receptor and Phosphorylation Mol. Cell. Biol., October 1, 2007; 27(19): 6913 - 6932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yuan and J. Xu Loss-of-Function Deletion of the Steroid Receptor Coactivator-1 Gene in Mice Reduces Estrogen Effect on the Vascular Injury Response Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1521 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hosoda, M. Hiroyama, A. Sanbe, J.-i. Birumachi, T. Kitamura, S. Cotecchia, P. C. Simpson, G. Tsujimoto, and A. Tanoue Blockade of both {alpha}1A- and {alpha}1B-adrenergic receptor subtype signaling is required to inhibit neointimal formation in the mouse femoral artery Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H514 - H519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C-K. Chung, S. Zhou, L. Liao, J. C.-Y. Tien, N. M. Greenberg, and J. Xu Genetic Ablation of the Amplified-in-Breast Cancer 1 Inhibits Spontaneous Prostate Cancer Progression in Mice Cancer Res., June 15, 2007; 67(12): 5965 - 5975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wierman and W. M. Kohrt Review Article: Vascular and Metabolic Effects of Sex Steroids: New Insights Into Clinical Trials Reproductive Sciences, May 1, 2007; 14(4): 300 - 314. [Abstract] [PDF]
|
|
|
|
 |
|
 H. J. Li, Z. Haque, Q. Lu, L. Li, R. Karas, and M. Mendelsohn Steroid receptor coactivator 3 is a coactivator for myocardin, the regulator of smooth muscle transcription and differentiation PNAS, March 6, 2007; 104(10): 4065 - 4070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mussi, C. Yu, B. W. O'Malley, and J. Xu Stimulation of Steroid Receptor Coactivator-3 (SRC-3) Gene Overexpression by a Positive Regulatory Loop of E2F1 and SRC-3 Mol. Endocrinol., December 1, 2006; 20(12): 3105 - 3119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Mussi, L. Liao, S.-E. Park, P. Ciana, A. Maggi, B. S. Katzenellenbogen, J. Xu, and B. W. O'Malley Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland PNAS, November 7, 2006; 103(45): 16716 - 16721. [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]
|
|
|
|
|
|
C. Bolego, E. Vegeto, C. Pinna, A. Maggi, and A. Cignarella Selective Agonists of Estrogen Receptor Isoforms: New Perspectives for Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2192 - 2199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Jeong, I. Kwak, K. Y. Lee, L. D. White, X.-P. Wang, F. C. Brunicardi, B. W. O'Malley, and F. J. DeMayo The Genomic Analysis of the Impact of Steroid Receptor Coactivators Ablation on Hepatic Metabolism Mol. Endocrinol., May 1, 2006; 20(5): 1138 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Yi, R.-C. Wu, J. Sandquist, J. Wong, S. Y. Tsai, M.-J. Tsai, A. R. Means, and B. W. O'Malley Peptidyl-Prolyl Isomerase 1 (Pin1) Serves as a Coactivator of Steroid Receptor by Regulating the Activity of Phosphorylated Steroid Receptor Coactivator 3 (SRC-3/AIB1) Mol. Cell. Biol., November 1, 2005; 25(21): 9687 - 9699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Igarashi-Migitaka, A. Takeshita, N. Koibuchi, S. Yamada, R. Ohtani-Kaneko, and K. Hirata Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis Eur. J. Endocrinol., October 1, 2005; 153(4): 595 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Paul, D. R. Buchholz, L. Fu, and Y.-B. Shi Tissue- and Gene-specific Recruitment of Steroid Receptor Coactivator-3 by Thyroid Hormone Receptor during Development J. Biol. Chem., July 22, 2005; 280(29): 27165 - 27172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mendelsohn and R. H. Karas Molecular and Cellular Basis of Cardiovascular Gender Differences Science, June 10, 2005; 308(5728): 1583 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, S.-Q. Kuang, L. Liao, S. Zhou, and J. Xu Haploid Inactivation of the Amplified-in-Breast Cancer 3 Coactivator Reduces the Inhibitory Effect of Peroxisome Proliferator-Activated Receptor {gamma} and Retinoid X Receptor on Cell Proliferation and Accelerates Polyoma Middle-T Antigen-Induced Mammary Tumorigenesis in Mice Cancer Res., October 1, 2004; 64(19): 7169 - 7177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goel and R. Janknecht Concerted Activation of ETS Protein ER81 by p160 Coactivators, the Acetyltransferase p300 and the Receptor Tyrosine Kinase HER2/Neu J. Biol. Chem., April 9, 2004; 279(15): 14909 - 14916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mark, H. Yoshida-Komiya, M. Gehin, L. Liao, M.-J. Tsai, B. W. O'Malley, P. Chambon, and J. Xu Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction PNAS, March 30, 2004; 101(13): 4453 - 4458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, H. Zhang, A. V. Lee, B. W. O'Malley, and J. Xu AIB1/SRC-3 Deficiency Affects Insulin-Like Growth Factor I Signaling Pathway and Suppresses v-Ha-ras-induced Breast Cancer Initiation and Progression in Mice Cancer Res., March 1, 2004; 64(5): 1875 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu and Q. Li Review of the in Vivo Functions of the p160 Steroid Receptor Coactivator Family Mol. Endocrinol., September 1, 2003; 17(9): 1681 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, L. Liao, S.-Q. Kuang, and J. Xu Spatial Distribution of the Messenger Ribonucleic Acid and Protein of the Nuclear Receptor Coactivator, Amplified in Breast Cancer-3, in Mice Endocrinology, April 1, 2003; 144(4): 1435 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, H. Zhang, F. A. Pereira, Y. Yuan, F. J. DeMayo, L. Ko, and J. Xu Deletion of the Cancer-amplified Coactivator AIB3 Results in Defective Placentation and Embryonic Lethality J. Biol. Chem., November 15, 2002; 277(47): 45356 - 45360. [Abstract] [Full Text] [PDF]
|
|