L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer.
ABSTRACT To find reliable biomarkers for high-grade malignancy, the relationship between immunohistochemical L-type amino-acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki-67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and <0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis.
International Journal of Pharmaceutics 10/2013; 455(1-2):394-395. DOI:10.1016/j.ijpharm.2013.07.052 · 3.79 Impact Factor
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ABSTRACT: L-type amino acid transporter 1 (LAT1), the first isotype of amino acid transport system L, transports aromatic and branched amino acids pivotal for fundamental cellular activities such cellular growth and proliferation. LAT1 expression was high only in the brain in contrast to its limited distribution and low level of expression in normal tissues. We found potent LAT1 expression in canine caput epididymis by quantitative RT-PCR and Western blotting analysis. Immnuno-histochemical examination revealed observable LAT1 in microvillous epithelial cells.Journal of Veterinary Medical Science 09/2014; 77(1). DOI:10.1292/jvms.14-0014 · 0.88 Impact Factor
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ABSTRACT: The altered metabolism of cancer cells is a treasure trove to discover new anti-tumoral strategies. The gene (SLC7A5) encoding System L amino acid transporter 1 (LAT1) is over-expressed in murine lymphoma cells generated via T cell deletion of the pten tumor suppressor, and also in human T-cell Acute lymphoblastic leukemia (T-ALL)/lymphoma (T-LL) cells. We show here that a potent and LAT1 selective inhibitor (JPH203) decreased leukemic cell viability and proliferation, induced transient autophagy followed by apoptosis. JPH203 could also alter the in vivo growth of luciferase-expressing-tPTEN-/- cells xenografted into nude mice. In contrast, JPH203 was non-toxic to normal murine thymocytes and human peripheral blood lymphocytes. JPH203 interfered with constitutive activation of mTORC1 and Akt, decreased expression of c-myc and triggered an Unfolded Protein Response mediated by the CHOP transcription factor associated with cell death. A JPH203-resistant tPTEN-/- clone appeared CHOP induction deficient. We also demonstrate that targeting LAT1 may be an efficient broad spectrum adjuvant approach to treat deadly T-cell malignancies as the molecule synergized with rapamycin, dexamethasone, doxorubicin, velcade and L-asparaginase to alter leukemic cell viability.Leukemia accepted article preview online, 08 December 2014. doi:10.1038/leu.2014.338.Leukemia 12/2014; DOI:10.1038/leu.2014.338 · 9.38 Impact Factor