Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.
Bottom Line: Among aromatic amino acid transporters, ATB(0,+), LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively.Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB(0,+) became significant at 1000 μM, accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells.ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo.
Affiliation: Division of Bio-system Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan.Show MeSH
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Mentions: LAT2 expression is associated with normal tissues, whereas LAT1 and ATB0,+ are known for their relevance to malignant tumors.6,9,20 To assess the contribution of LAT1 and ATB0,+ in BPA uptake, uptake rates were measured in cancer cell lines with various expression levels of LAT1 and ATB0,+. The LAT1 protein amounts were compared in Western blot analysis: low in FLC-4, medium in MCF-7 and MIA PaCa-2, and high in HeLa S3 and T3M4 cells (Fig.5a). In contrast, ATB0,+ protein was strongly detected in MCF-7 and also weakly in T3M4 cells, but not in the other cell lines (Fig.5b). The BPA uptake rates were proportional to the LAT1 protein levels (Fig.5a,c). We examined the Na+-dependence of BPA uptake, because ATB0,+ is Na+-dependent whereas LAT1 is not. There were no significant differences in the uptakes at 100 μM BPA between Na+-free and normal Na+ conditions (Fig.5c).
Affiliation: Division of Bio-system Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan.