This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Chen, H. Articles by Adams, J. S. Search for Related Content PubMed PubMed Citation Articles by Chen, H. Articles by Adams, J. S.

Creation of Estrogen Resistance in Vivo by Transgenic Overexpression of the Heterogeneous Nuclear Ribonucleoprotein-Related Estrogen Response Element Binding Protein

Burns and Allen Research Institute and Division of Endocrinology, Diabetes, and Metabolism (H.C., L.N., G.H., J.S.A.) and Department of Pathology (B.H.), Cedars-Sinai Medical Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90048; Department of Surgery (W.S.), The University of Cincinnati College of Medicine, Cincinnati, Ohio 45267; and Department of Pathology (T.L.C.), University of Alabama at Birmingham, Birmingham, Alabama 35294

Address all correspondence and requests for reprints to: Hong Chen, Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room B-131, Los Angeles, California 90048. E-mail: chenh{at}cshs.org.

Estrogen unresponsiveness among primate species can result from overexpression of a heterogeneous nuclear ribonucleoprotein (hnRNP) that competes with estrogen receptor (ER) for binding to the estrogen-response element (ERE). This hnRNP has been coined the "ERE-binding protein" (ERE-BP). The ERE-BP is a member of the hnRNP C-like subfamily of hnRNPs, traditionally considered to be single-strand RNA binding proteins designed for the stabilization and handling of pre-mRNA. To verify in vivo the dominant-negative actions of the ERE-BP to inhibit ER-ERE-directed transactivation and to avoid the potential for lethality from global overexpression of an hnRNP, we generated transgenic mice that overexpressed ERE-BP in breast tissue under the control of a whey acidic protein gene promoter. Graded overexpression of ERE-BP in transgenic mice was established. Founders were viable and fertile. Female transgenics in all lines gave birth to pups, but their ability to nurse was dependent on the level of ERE-BP expression in breast; high-ERE-BP expressors were unable to lactate. A gradient of impaired breast pheno(histo)type, from near normal to failed ductal development and lactational capacity, correlated with the relative level of transgene expression. ERE-BP, expressed either endogenously as a transgene or after transfection, colocalized with ER in the nucleus of target cells. This work confirms that tissue-targeted overexpression of the ERE-BP can effectively block estrogen-ER-ERE-directed action in vivo.

This article has been cited by other articles:

				H. Chen, M. Hewison, and J. S. Adams Control of Estradiol-Directed Gene Transactivation by an Intracellular Estrogen-Binding Protein and an Estrogen Response Element-Binding Protein Mol. Endocrinol., March 1, 2008; 22(3): 559 - 569. [Abstract] [Full Text] [PDF]