Bioconcentration Hypothesis: Potential Role of Transporter in Breast Ductules

摘要

Hope for prevention of breast cancer arises form international breast cancer rate variation, which suggests potentially modifiable environmental determinants of the disease. We used immunocytochemical and Western blot methods to localize two membrane xenobiotic transporter, MRPl and MRP2. MRP2 is located at the apical membrane of epithelial cells and excretes anionic hydrophobic substrates, such as 17 beta-estrogen glucuronide, antioxidants, and toxic molecules into lumen of the kidney, liver, and gut. In isolated and tissue cultured breast ductules, MRP2 is located predominantly I the apical region of luminal epithelial cells and thus might bioconcentrate toxic substrates into sealed, non-flushed lumens. In a comparison epithelium, Caco2 cells in culture, MRP2 is localized at the apical membrane only and is detected as bands at 60 and 190 kDa in blots, but in breast tissue cultures MRP2 is detected only at 60 kDa. MRPl transports anionic hydrophobic molecules across the basolateral side of epithelial cells into the connective tissue. In isolated and tissue cultured breast ductules, MRPl is localized in the cytoplasm, as is typical for numerous epithelial cells and is detected as a band at 190 kDa. Thus, overall transport of toxins to, and bioconcentration in, breast ductile lumens may be determined by a balance between these two transporters. We have also obtained a new critical piece of information: we have detected the mRNA for MRP2 in samples of breast reduction tissue.