First Author | Chen H | Year | 2005 |
Journal | Endocrinology | Volume | 146 |
Issue | 10 | Pages | 4266-73 |
PubMed ID | 15976060 | Mgi Jnum | J:101554 |
Mgi Id | MGI:3604257 | Doi | 10.1210/en.2005-0160 |
Citation | Chen H, et al. (2005) Creation of estrogen resistance in vivo by transgenic overexpression of the heterogeneous nuclear ribonucleoprotein-related estrogen response element binding protein. Endocrinology 146(10):4266-73 |
abstractText | 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 ERalpha in the nucleus of target cells. This work confirms that tissue-targeted overexpression of the ERE-BP can effectively block estrogen-ERalpha-ERE-directed action in vivo. |