Abstract
BackgroundThe system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer.MethodsTo clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting.ResultsExpression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors.ConclusionsThese findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.
Highlights
The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer
In order to take into account possible inter-individual variation in the expression of LAT family (LAT1, LAT2, LAT3, LAT4, and 4F2hc) mRNAs and phosphorylated S6 ribosomal protein (Ser-235/236), tumor tissue samples and the corresponding non-tumor tissue samples obtained from the same patient were compared
We investigated the correlation between LAT1 mRNA and phosphorylated
Summary
The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. The system large amino acid transporter (LAT) is a major nutrient transport system that is responsible for Na+-independent transport of large neutral amino acids [9,10] It plays a critical role in the absorption of amino acids from the small intestine, as well as in movement of amino acids across the blood–brain barrier, the placenta, and the proximal tubules of the kidneys [6,7]. LAT1 may play a key role in the growth of tumor cells by promoting the uptake of essential amino acids. The LAT1specific inhibitor JPH203 (KYT0353) was reported to reduce the incorporation of essential amino acids by cancer cell lines and to attenuate the growth of human tumor cells implanted into nude mice [17], indicating that LAT1 might be an attractive target for cancer therapy
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