Abstract
Estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. On the other hand, steroid and xenobiotic receptor (SXR) regulates the expression of the cytochrome P-450 3A (CYP3A) gene family. It has been reported that SXR is expressed in breast cancer cells. To study whether SXR affects on estrogen action, we performed transient transfection-based reporter assays. SXR potentiated ER-mediated transcription in the presence of estradiol in MCF-7 breast cancer cells. To study the mechanism of SXR potentiation on ER-mediated transcription, we performed GST pull down, mammalian two hybrid, and electropholetic mobility shift assays. We showed that (i) SXR did not bind with ER, (ii) SXR did not bind to ERE. Thus, we focused on the effect of SXR on the binding between ER and corepressors. In reporter assays, silencing mediator for retinoid and thyroid receptors (SMRT) reversed the potentiation of ER activity by SXR. The SMRT was dissociated from ER by SXR in a receptor concentration-dependent manner. These results suggest that SXR induced ER-mediated transcription by squelching limiting amounts of SMRT. In conclusion, our results indicated that SXR induces ER signaling, which may play crucial role for cell growth, cell differentiation in breast cancer cells. [J Physiol Sci. 2006;56 Suppl:S218]
