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XB-ART-1752
Biochem Biophys Res Commun 2005 Aug 05;3333:754-62. doi: 10.1016/j.bbrc.2005.05.174.
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Characterization of the organic cation transporter SLC22A16: a doxorubicin importer.

Okabe M , Unno M , Harigae H , Kaku M , Okitsu Y , Sasaki T , Mizoi T , Shiiba K , Takanaga H , Terasaki T , Matsuno S , Sasaki I , Ito S , Abe T .


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Specific efflux transporters, such as P-glycoprotein, have been shown to confer drug resistance by decreasing the intracellular accumulation of anticancer drugs. Understanding influx transporters, as well as efflux transporters, is essential to overcome this resistance. We report the expression profile and pharmacological characterization of an organic cation transporter, SLC22A16. The results of our experiments indicate that SLC22A16 is a mediator of doxorubicin uptake in cancer cells. Quantitative real-time RT-PCR analyses show that SLC22A16 is expressed in primary samples taken from patients with acute leukemia. Xenopus oocytes injected with SLC22A16 cRNA import doxorubicin, a widely used anticancer drug for hematological malignancies, in a saturable and dose-dependent manner. The apparent Km value for doxorubicin import was 5.2+/-0.4 microM. In cytotoxic assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16 cells became significantly more sensitive to doxorubicin (2 microM) treatment. Characterization of SLC22A16 will help in designing novel therapies targeting hematological malignancies.

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Species referenced: Xenopus
Genes referenced: slc22a16