Effects of PCBs on nuclear receptors-mediated transcription in breast cancer cells

Abstract

Polychlorinated biphenyls (PCBs) are environmental chemicals that may cause a series of abnormal effects. Due to its stability and lipophilicity, they are accumulated in liver and/or adipose tissues. It has been speculated that PCB may associate with the generation and development of breast cancer. Thus, we focused on the effect of PCBs on estrogen rceptor (ER)- or progesterone receptor (PR)-mediated transcription using transient transfection-based reporter assays. In CV-1 cells, hydroxylated (OH)-PCB activated the estradiol (E2)-induced ER-mediated transcription in a dose dependent manner at concentration from 10⁻¹² to 10⁻⁹ M. However, the transcriptional activity is suppressed at higher concentrations. The magnitude of induction was about 2.5 fold compare to the level without PCB. On the other hand, no significant difference was observed when PR was cotransfected in the presence of OH-PCB. Since steroid and xenobiotic receptor (SXR) potentiated the ER-mediated transcription (Rokutanda et al, personal communication), we also investigated the effect of PCBs on SXR-induced ER-mediated transcription. OH-PCB further activated the transcription in both CV-1 and MCF-7 breast cancer derived cells. These results indicate that PCBs potentiated the ER-mediated transcription in breast cancer cells. In conclusion, PCB may associate with the production and development of breast cancer. [J Physiol Sci. 2006;56 Suppl:S219]