Limiting effects of RIP140 in estrogen signaling: potential mediation of anti-estrogenic effects of retinoic acid
| Autor: | Kristina A, White, Mark M, Yore, Dexin, Deng, Michael J, Spinella |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cell Nucleus
Dose-Response Relationship Drug Cell Cycle Nuclear Proteins Estrogens Tretinoin Blotting Northern Ligands Transfection Nuclear Receptor Interacting Protein 1 Receptors Estrogen Genes Reporter Cell Line Tumor Humans Gene Silencing RNA Small Interfering Luciferases Adaptor Proteins Signal Transducing Cell Proliferation Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 280(9) |
| ISSN: | 0021-9258 |
| Popis: | The receptor interacting protein 140 (RIP140) belongs to a unique subclass of nuclear receptor coregulators with the ability to bind and repress the action of a number of agonist-bound hormone receptors. We have previously demonstrated that all-trans-retinoic acid (RA) induction of RIP140 constitutes a rate-limiting step in the regulation of retinoid receptor signaling. Here we demonstrate that RIP140 is also a limiting regulator of estrogen receptor signaling. Overexpression of RIP140 dose dependently inhibits estrogen-dependent reporter activity in human breast cancer cells. Furthermore, small interfering RNA to RIP140 enhances estrogen-dependent signaling. Our previous studies indicate that RIP140 is a direct target of RA. We report here that RA can abrogate estrogen-mediated cell cycle re-entry. In addition, RA treatment of estrogen-dependent breast cancer cells opposes estrogen receptor-dependent reporter activity, implying that a proportion of RA effects are anti-estrogenic. We provide evidence for a role for RIP140 in mediating anti-estrogenic effects of RA. RIP140 small interfering RNA blocks RA-mediated repression of estrogen receptor activity and provides a growth advantage to estrogen-dependent cells. Together these data implicate a regulatory role for RIP140 in mediating anti-estrogenic effects of RA in estrogen-dependent breast cancer cells and suggest that acute regulation of coregulator expression may be a general mechanism to integrate diverse hormone signals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|