RETRACTED: The tamoxifen-responsive estrogen receptor α mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes (Retracted Article)

The effects of estrogen and anti-estrogen are mediated through the estrogen receptors ER alpha and beta, which function as ligand-induced transcriptional factors. The nonsteroidal anti-estrogen tamoxifen is the most commonly used endocrine in the treatment of all stages of breast cancer in both pre- and postmenopausal women. Several lines of evidence have indicated that tamoxifen promotes association between ER alpha and corepressors N-Cor or silencing mediator for retinoid and thyroid hormone receptor (SMRT). Our results indicate that N-CoR/SMRT recognize and interact with helices H3 and H5 of the ER alpha ligand-binding domain in a 4-hydroxy tamoxifen-dependent manner. The mutant ER alpha (D351Y), derived from a tamoxifen-stimulated tumor and containing an amino acid substitution at position 351 within H3, showed reduced interaction with N-CoR/SMRT and high tamoxifen-induced activation function-1 (AF-1) activity. While the estradiol-dependent transcriptional activity of ER alpha (D351Y) was almost equal to that of wild-type ER alpha, the mutant exhibited higher levels of transcriptional activity in the presence of both E2 and 4-hydroxy tamoxifen compared with wild-type ER alpha. These results may explain the observation that the growth of tumor cells expressing ER alpha (D351Y) can be stimulated by tamoxifen, E2, or both.