Induction of nuclear receptor-mediated transcription by polychlorinated biphenyl (PCB) in breast cancer cells

Abstract

It is known that estrogen and estrogen receptor (ER) are related to progression and differentiation of breast cancer. Steroid and xenobiotic receptor (SXR) regulates target genes including Cytochrome P450 monooxygenase 3A4 (CYP3A4). Recently, it has been reported that SXR is expressed in breast cancer cells. In addition, we reported that SXR augments the ERα-mediated transcription. Polychlorinated biphenyls (PCBs) have been known as environmental chemicals that cause various effects on endocrine system or associate with the production of carcinomas. Using transient transfection-based reporter gene assays, we showed that PCB augmented the SXR-mediated transcription in MCF7 breast cancer cells but not in CV-1 cells. ERα did not affect the SXR-mediated transcription in CV-1cells. Combination of PCB and SXR additively induced the ERα-mediated transcription. Cofactors including steroid receptor coactivator-1 (SRC-1), SRC-3, silencing mediator for retinoid and thyroid hormone receptors (SMRT) and nuclear receptor corepressor (N-CoR) were excluded from the alternation of cofactor bindings to SXR using a series of mammalian two-hybrid assays. These results indicate that unknown factors in MCF7 cells may be required to the augmentation by PCB. Induction by PCBs may result in disruption of drug metabolism, in addition to native endocrine systems. [J Physiol Sci. 2007;57 Suppl:S171]