دورية
The AF-2 Region of the Retinoic Acid Receptor α Mediates Retinoic Acid Inhibition of Estrogen Receptor Function in Breast Cancer Cells*
| العنوان: | The AF-2 Region of the Retinoic Acid Receptor α Mediates Retinoic Acid Inhibition of Estrogen Receptor Function in Breast Cancer Cells* |
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| المؤلفون: | Pratt, M. A. Christine, Deonarine, Dave, Teixeira, Christine, Novosad, Denise, Tate, Bonnie F., Grippo, Joseph F. |
| المصدر: | Journal of Biological Chemistry; August 1996, Vol. 271 Issue: 34 p20346-20352, 7p |
| مستخلص: | The growth of estrogen receptor (ER)-positive breast cancer cells is inhibited by all-trans-retinoic acid (RA). In the present study, estrogen (E2) induction of pS2 mRNA levels was significantly reduced within 6 h following cotreatment with RA. In transient transfection experiments, RA repressed transactivation from a vitellogenin E2-responsive element by approximately 50% and wild-type RA receptor α (RARα) or RARβ enhanced this inhibition. Transfection of truncated RARα mutants terminating before or at amino acid 412 markedly decreased RA inhibition of E2-induced reporter gene activity. Expression of RARs with deletions of amino acids 413 and 414 in the transactivation-2 (AF-2) domain also reduced RA inhibition, while deletions and point mutations beyond amino acid 414 behaved like the wild-type RARα. RA-treated MCF-7 cells transfected with an RARα AF-2 region mutant were twice as sensitive to growth inhibition as untransfected and vector-transfected control cells. Thus, the AF-2 domain in the C terminus of the RARα mediates RA inhibition of ER-induced transcription in breast cancer cells. In addition, transcriptional interference between RARs and ERs may contribute to RA inhibition of ER-positive breast cancer cell growth. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00219258 1083351X |
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| DOI: | 10.1074/jbc.271.34.20346 |