Role of the l -amino Acid Transporter-1 (LAT-1) in Mouse Trophoblast Cell Invasion

Abstract LAT-1 (L-type amino acid transporter 1) is a system L, Na+ -independent amino acid transporter responsible for transport of large neutral amino acids. Dysregulated expression of LAT-1 is characteristic of many primary human cancers and it's over expression is related to tumor invasion....

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Bibliographic Details
Published in:Placenta (Eastbourne) 2010-06, Vol.31 (6), p.528-534
Main Authors: Chrostowski, M.K, McGonnigal, B.G, Stabila, J.P, Padbury, J.F
Format: Article
Language:English
Subjects:
Amino Acid Transport System y+ - genetics
Amino Acid Transport System y+ - metabolism
Analysis of Variance
Animals
Biological and medical sciences
Blotting, Western
Cells, Cultured
Down-Regulation - drug effects
Down-Regulation - genetics
Embryology: invertebrates and vertebrates. Teratology
Fundamental and applied biological sciences. Psychology
Gene Expression
Implantation
Internal Medicine
Invasion
L amino acid transporter
LAT-1
Leucine - pharmacology
Mice
Obstetrics and Gynecology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Small Interfering
Slc7a5
Stem Cells
Time Factors
Trophoblast stem cell
Trophoblasts - drug effects
Trophoblasts - metabolism
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Summary:Abstract LAT-1 (L-type amino acid transporter 1) is a system L, Na+ -independent amino acid transporter responsible for transport of large neutral amino acids. Dysregulated expression of LAT-1 is characteristic of many primary human cancers and it's over expression is related to tumor invasion. LAT-1 is highly expressed in the trophoblast giant cells (TGCs) at the time of implantation. Since trophoblast giant cells are highly invasive during the process of endometrial implantation and placentation, LAT-1 may play a role in the invasive phenotype. Our objectives were to identify the effects of increased and decreased LAT-1 expression on mouse trophoblast invasion. We therefore examined the role of amino acid deprivation, pharmacologic blockade specific to leucine transport and gene silencing (siRNA) on LAT-1 expression and trophoblast cell invasion. We utilized mouse primary trophoblast stem (TS) cells. LAT-1 mRNA expression was quantified by real time qPCR, protein by Western blotting and cell invasion was measured in Transwell plates through Matrigel . Amino acid transport using uptake of tritiated leucine. Under limited leucine availability and/or pharmacologic blockage, LAT-1 gene expression was significantly increased, p < 0.05. This was associated with a 3-fold increase in cell invasion, p < 0.05. In contrast, following si RNA-mediated gene silencing decreased LAT-1 expression (both mRNA and protein) was associated with decreased cell invasion and decreased leucine uptake, p < 0.05. Upregulation of LAT-1 gene expression via limited amino acid availability or following pharmacologic blockade of transport leads to an increase in mouse trophoblast stem cell invasiveness. Downregulation of LAT-1 expression via genetic silencing leads to inhibition of invasiveness. These results demonstrate that LAT-1 plays an important role in trophoblast invasion.
ISSN:0143-4004
1532-3102
DOI:10.1016/j.placenta.2009.12.010