EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS ON THE PROGRESSION OF BREAST CANCER -ITAIMS AT THE DEVELOPMENT OF ANOVEL REMOVAL METHOD AND TREATMENT

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Polychlorinated biphenyls (PCBs) have been known as environmental chemicals that cause various effects on endocrine system and speculated the association with the production of carcinomas. Using reporter gene assays, we showed that PCB augmented the SXR-mediated transcription in MCF-7 breast cancer cells but not in CV-1 cells. On the other hand, in the presence of rifampicin, agonist of SXR, PCB augmented the transcription effectively at 10^<-11> M in CV-1 cells, but not in MCF-7 cells. ERα did not affect the transcription through SXRE in CV-1 cells. Cofactors including SRC-1, p/CIP, N-CoR and SMRT slightly altered bindings to SXR using a series of mammalian two-hybrid assays. These results indicate that the sum of subtle alterations of cofactor-SXR bindings by PCB may result in disruption of SXR-mediated transcription. In summary, SXR-mediated transcription induced by PCBs may result in disruption of local drug metabolism, in addition to native endocrine systems.