Characterization of 3-[125I]iodo-α-methyl-L-tyrosine transport via human L-type amino acid transporter 1

Shikano, Naoto; Kanai, Yoshikatsu; Kawai, Keiichi; Ishikawa, Nobuyoshi; Endou, Hitoshi

doi:10.1016/s0969-8051(02)00350-5

Cited by 37 publications

(38 citation statements)

References 25 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, we previously showed that a-methyl phenylalanine and a-methyl 3,4-dihydroxyphenylalanine and AMT inhibited L-14 C-leucine uptake mediated by LAT1, but they had less of an effect on LAT2 (22,24,25). Moreover, in the amphibian oocyte expression system, we observed that L-3-125 I-a-methyl tyrosine ( 125 I-IMT) is transported by LAT1 but not by LAT2 (27).…”

Section: Discussionsupporting

confidence: 82%

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Wiriyasermkul¹,

Nagamori²,

Tominaga³

et al. 2012

J Nucl Med

Self Cite

124

114

View full text Add to dashboard Cite

L-3-18 F-a-methyl tyrosine ( 18 F-FAMT) has been developed as a PET radiotracer for tumor imaging. Clinical studies have demonstrated the usefulness of 18 F-FAMT PET for the prediction of prognosis and the differentiation of malignant tumors and benign lesions. 18 F-FAMT exhibits higher cancer specificity in peripheral organs than other amino acid PET tracers and 18 F-FDG. The accumulation of 18 F-FAMT is strongly correlated with the expression of L-type amino acid transporter 1 (LAT1), an isoform of system L highly upregulated in cancers. In this study, we examined the interaction of 3-fluoro-L-a-methyltyrosine (FAMT) with amino acid transporters to assess the mechanisms of 18 F-FAMT uptake in PET. Methods: We applied in vitro assays using established mammalian cell lines stably expressing LAT1 or a non-cancer-type system L isoform LAT2. The inhibitory effect on L-14 C-leucine uptake and the induction effect on efflux of preloaded L-14 C-leucine were examined for FAMT and other amino acid tracers. FAMT transport was compared among cell lines with varied LAT1 expression level. Results: FAMT prominently inhibited LAT1-mediated L-14 C-leucine uptake in a competitive manner but had less of an effect on LAT2. In the efflux experiments, FAMT induced the efflux of preloaded L-14 C-leucine through LAT1, indicating that FAMT is transported by LAT1 and not by LAT2. Among amino acid-related compounds examined in this study, including those used for PET tracers, the compounds with an a-methyl group such as FAMT, 2-fluoro-L-a-methyl-tyrosine, 3-iodo-L-a-methyl-tyrosine, and L-a-methyl-tyrosine were well transported by LAT1 but not by LAT2. However, L-methionine, L-tyrosine, 3-fluoro-L-tyrosine, 2-fluoro-L-tyrosine, and O-(2-fluoroethyl)-L-tyrosine were transported by both LAT1 and LAT2, suggesting that the a-methyl moiety is responsible for the LAT1 selectivity of FAMT. FAMT transport rate and LAT1 protein level were well correlated, supporting the importance of LAT1 for the cellular uptake of FAMT. Conclusion: Distinct from other amino acid PET tracers, because of its a-methyl moiety, FAMT is selective to LAT1 and not transported by LAT2. This property of FAMT is proposed to contribute to highly tumorspecific accumulation of 18 F-FAMT in PET.

show abstract

Section: Discussionsupporting

confidence: 82%

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Wiriyasermkul¹,

Nagamori²,

Tominaga³

et al. 2012

J Nucl Med

Self Cite

124

114

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that in cultured human glioma cells, membrane transport of IMT is dominated by BCH-sensitive transport system, LAT1. 20,21 LAT1-mediated IMT transport and 4F2 antigen expression are dependent on proliferation rate of human glioma cells in vitro and are significantly correlated to each other. 20 These data give further support to the involvement of the LAT1 in cell proliferation.…”

Section: Discussionmentioning

confidence: 98%

L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors

Nawashiro

Otani

Shinomiya

et al. 2006

Intl Journal of Cancer

Self Cite

214

241

View full text Add to dashboard Cite

L-type amino acid transporter 1 (LAT1) is a Na 1 -independent neutral amino acid transport agency and essential for the transport of large neutral amino acids. LAT1 has been identified as a light chain of the CD98 heterodimer from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells. We have investigated for the first time, the expression of the transporter in the human primary astrocytic tumor tissue from 60 patients. LAT1 is unique because it requires an additional single membrane spanning protein, the heavy chain of 4F2 cell surface antigen (4F2hc), for its functional expression. 4F2hc expression was also determined by immunohistochemistry. Kaplan-Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole (p < 0.0001) and for those with glioblastoma multiforme in particular (p 5 0.0001). Cox regression analyses demonstrated that LAT1 expression was one of significant predictors of outcome, independent of all other variables. On the basis of these findings, we also investigated the effect of the specific inhibitor to LAT1, 2-aminobicyclo-2 (2,2,1)-heptane-2-carboxylic acid (BCH), on the survival of C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH inhibited the growth of C6 glioma cells in vitro and in vivo in a dose-dependent manner. KaplanMeier survival data of rats treated with BCH were significant. These findings suggest that LAT1 could be one of the molecular targets in glioma therapy. ' 2006 Wiley-Liss, Inc.

show abstract

“…Similar to LAT3 (15), L-leucinol and L-valinol, which have a hydroxymethyl group instead of a ␣-carboxyl group, also inhibit the uptake of L-phenylalanine. Methyltyrosine, a LAT1-specific inhibitor (27), is a poor inhibitor of LAT4 (Fig. 4a).…”

Section: Identification Of Lat4 -Lat3mentioning

confidence: 99%

Identification of LAT4, a Novel Amino Acid Transporter with System L Activity

Bodoy¹,

Martín²,

Zorzano

et al. 2005

Journal of Biological Chemistry

221

218

View full text Add to dashboard Cite

System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chlorideand pH-independent, is not trans-stimulated, and shows two kinetic components. The low affinity component of LAT4 induced activity is sensitive to the sulfhydryl-specific reagent N-ethylmaleimide but not that with high affinity. Mutation in LAT4 of the SLC43 conserved serine 297 to alanine abolishes sensitivity to N-ethylmaleimide. LAT4 activity is detected at the basolateral membrane of PCT kidney cells. In situ hybridization experiments show that LAT4 mRNA is restricted to the epithelial cells of the distal tubule and the collecting duct in the kidney. In the intestine, LAT4 is mainly present in the cells of the crypt.

show abstract

Characterization of 3-[125I]iodo-α-methyl-L-tyrosine transport via human L-type amino acid transporter 1

Abstract: We examined transport of 3-

Cited by 37 publications

References 25 publications

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

L‐type amino acid transporter 1 as a potential molecular target in human astrocytic tumors

Identification of LAT4, a Novel Amino Acid Transporter with System L Activity

Contact Info

Product

Resources

About