title: Expression and localization of the uptake transporters OATP2B1, OATP3A1 and OATP5A1 in non-malignant and malignant breast tissue.
abstract: Organic anion transporting polypeptides (OATPs, gene family SLCO/SLC21) mediate the uptake of multiple endogenous substances such as estrogens and estrogen metabolites and of several widely prescribed drugs (e.g. statins, antibiotics and anticancer agents) into cells. Since several anticancer agents have been identified as substrates for OATPs, these transporters may also have an impact on cancer treatment. Expression of OATPs has been identified in colon, pancreatic and gastric carcinomas but to date little is known about the expression and localization of OATP family members in non-malignant breast tissue and breast cancer. We therefore analyzed the mRNA expression of all human OATP family members and further evaluated the mRNA amount of the highly-expressed OATPs OATP2B1, OATP3A1 and OATP5A1 in 10 paired samples of normal breast tissue and breast cancer. Furthermore, the tissue-specific localization of these OATPs was investigated. The results demonstrated that the mRNA expression of OATPs in normal and malignant breast tissue shows a high interindividual variability and that no significant differences in the mRNA amount between normal and malignant tissue could be detected. Furthermore, we localized OATP3A1 and OATP5A1 to the plasma membrane of epithelial cells of the lactiferous ducts in normal breast tissue. In breast cancer, both OATPs are highly expressed in the plasma membrane and in the cytoplasm. Since estrogen and estrogen metabolites as well as anticancer agents are substrates for OATPs these results indicate the possibility of OATP-mediated uptake of hormones during breast cancer development and an impact of certain OATPs on chemotherapeutic cancer treatment.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Kindla
authors.forename: Tilman T
authors.initials: TT
authors.lastname: Rau
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jung
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Reiner
authors.initials: R
authors.lastname: Strick
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fromm
authors.forename: Jörg
authors.initials: J
authors.lastname: König
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004967:Estrogens; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C450859:SLCO2B1 protein, human; C479544:SLCO3A1 protein, human; C551029:SLCO5A1 protein, human